Lnc2Meth: a manually curated database of regulatory relationships between long non-coding RNAs and DNA methylation associated with human disease.

Lnc2Meth (http://www.bio-bigdata.com/Lnc2Meth/), an interactive resource to identify regulatory relationships between human long non-coding RNAs (lncRNAs) and DNA methylation, is not only a manually curated collection and annotation of experimentally supported lncRNAs-DNA methylation associations but also a platform that effectively integrates tools for calculating and identifying the differentially methylated lncRNAs and protein-coding genes (PCGs) in diverse human diseases. The resource provides: (i) advanced search possibilities, e.g. retrieval of the database by searching the lncRNA symbol of interest, DNA methylation patterns, regulatory mechanisms and disease types; (ii) abundant computationally calculated DNA methylation array profiles for the lncRNAs and PCGs; (iii) the prognostic values for each hit transcript calculated from the patients clinical data; (iv) a genome browser to display the DNA methylation landscape of the lncRNA transcripts for a specific type of disease; (v) tools to re-annotate probes to lncRNA loci and identify the differential methylation patterns for lncRNAs and PCGs with user-supplied external datasets; (vi) an R package (LncDM) to complete the differentially methylated lncRNAs identification and visualization with local computers. Lnc2Meth provides a timely and valuable resource that can be applied to significantly expand our understanding of the regulatory relationships between lncRNAs and DNA methylation in various human diseases.

Histone variant H3.3 and its functions in reprogramming.

Histones are a class of evolutionarily conserved nuclear proteins. Histone octamer wrapped by DNA sequence forms the nucleosome, the basic building blocks of eukaryotic chromatin. The nucleosomes keep the DNA in a condensed state, maintain the integrity of the genome, and ensure proper DNA replication, transcription, recombination and repair. Nucleosomes can regulate the biological processes of the cell through a number of distinct post-translational modifications (PTMs) and turnovers of histone variants. Although the histone H3 variant H3.3 differs from the canonical histone H3 by only a few amino acids, it could be incorporated into distinct chromatin regions by specific chaperones and exert diverse functions on the chromatin. Importantly, H3.3 is also an essential maternal factor, and plays a key role in cellular reprogramming during fertilization and somatic cell nuclear transfer. In this review, we summarize the structural properties and enrichment pattern of H3.3, and explore the specific chaperones involved in the H3.3-mediated cellular reprogramming. We hope to provide some insights on new means to improve the efficiency of somatic cell reprogramming and lay the foundation for its potential applications.

Morphological changes and germ layer formation in the porcine embryos from days 7-13 of development.

Morphogenesis and identification of embryonic differentiation in porcine embryos are crucial issues for developmental biology and laboratory animal science. The current paper presents a study on the asynchronous development of hatched porcine embryos from days 7 to 13 post-insemination. Examination of semi-thin sections of the hypoblast showed that it had characteristics similar to those of the mouse anterior visceral endoderm during embryonic disc formation. Also, a cavity appeared in the epiblast, which was similar to a mouse proamniotic cavity. With the gradual disappearance of Rauber's layer, the cavity opened and contacted the external environment directly, all of which formed the embryonic disc. To confirm the differentiation characteristics, we performed immunohistochemical analyses and showed that GATA6 was detected clearly in parietal endoderm cells during embryonic disc establishment. OCT4 was expressed in the inner cell mass (ICM) and trophoblast of hatched blastocysts and in the epiblast during formation of the embryonic disc. However, OCT4 showed comparatively decreased expression in the posterior embryonic disc, primitive streak and migrating cells. SOX2 was present in the ICM and epiblast. Therefore, both SOX2 and OCT4 can be used as markers of pluripotent cells in the porcine embryonic disc. At the start of gastrulation, staining revealed VIMENTIN in the posterior of the embryonic disc, primitive streak and in migrating cells that underlay the embryonic disc and was also expressed in epiblast cells located in the anterior primitive streak. Together with serial sections of embryos stained by whole mount immunohistochemistry, the mesoderm differentiation pattern was shown as an ingression movement that took place at the posterior of the embryonic disc and with bilateral migration along the embryonic disc borders.

Adenosine receptor expression in a rat model of experimental autoimmune myasthenia gravis.

Extracellular adenosine is an essential negative regulator of immune reactions that acts by signaling via 4 distinct adenosine receptors. We evaluated adenosine receptor expression in Lewis rats presenting with experimental autoimmune myasthenia gravis (EAMG) to determine whether the expression of adenosine receptors are changed in the development and progression of EAMG. Lymphocyte A1AR and A2AAR mRNA and protein levels from lymphocytes harvested from the lymph nodes, spleen, and peripheral blood mononuclear cells (PBMCs) of EAMG rats were decreased. A modest but not significant increase in A2BAR levels was observed in EAMG lymphocytes harvested from lymph nodes and PBMCs. No changes in A3AR expression were observed in lymphocytes harvested from lymph nodes, spleen, or PBMCs following EAMG induction. Results presented in this report showed that the expression levels and the distribution pattern of adenosine receptors were altered in EAMG lymphocytes.

Lack of association between the G+2044A polymorphism of interleukin-13 gene and chronic obstructive pulmonary disease: a meta-analysis.

Numerous studies have investigated association of interleukin-13 (IL-13) G+2044A polymorphism with COPD susceptibility; however, the results were inconsistent and inconclusive. To evaluate the association between the IL-13 G+2044A polymorphism and susceptibility to COPD, a meta-analysis of published case-control studies was performed. Based on PubMed and Chinese database, this research selected studies that examined the association of the IL-13 G+2044A polymorphism with COPD. A genetic model-free approach was used to assess whether the combined data showed this association. Then a subgroup analysis was also performed, with stratifications for race, study design, and sample size. Six studies (total 1,213 COPD patients and 801 control subjects) for the IL-13 G+2044A polymorphism with COPD were included in the meta-analysis (G- vs A-allele: OR 1.12, 95 % CI 0.96-1.32, P = 0.15; genotypes GG+GA vs genotype AA: OR 0.99, 95 % CI 0.49-2.00, P = 0.98; genotype GG vs genotypes GA+AA: OR 1.18, 95 % CI 0.97-1.44, P = 0.09; genotype GA vs genotypes GG+AA: OR 0.85, 95 % CI 0.70-1.04, P = 0.11). This meta-analysis demonstrates that the IL-13 G+2044A polymorphism does not confer susceptibility to COPD. More detailed data about individual and environment, larger sample sizes with unbiased genotyping methods and matched controls in different populations are required.

Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity.

The adenosine A2A receptor (A2AR) is the major cellular adenosine receptor commonly associated with immunosuppression. Here, we investigated whether A2AR activation holds the potential for impacting the severity of experimental autoimmune myasthenia gravis (EAMG) induced following immunization of Lewis rats with the acetylcholine receptor (AChR) R97-116 peptide. This report demonstrates reduced A2AR expression by both T cells and B cells residing in spleen and lymph nodes following EAMG induction. A2AR stimulation inhibited anti-AChR antibody production and proliferation of AChR-specific lymphocytes in vitro. Inhibition was blocked with the A2AR antagonists or protein kinase A inhibitor. We also determined that the development of EAMG was accompanied by a T-helper cell imbalance that could be restored following A2AR stimulation that resulted in increased Treg cell levels and a reduction in Th1-, Th2-, and Th17-cell subtypes. An EAMG-preventive treatment regimen was established that consisted of (2-(p-(2-carbonylethyl)phenylethylamino)-5-N-ethylcarboxamidoadenosine) (CGS21680; A2AR agonist) administration 1 day prior to EAMG induction. Administration of CGS21680 29 days post EAMG induction (therapeutic treatment) also ameliorated disease severity. We conclude that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of myasthenia gravis or other T-cell- and B-cell-mediated autoimmune diseases.

Association between the interleukin-4, interleukin-13 polymorphisms and asthma: a meta-analysis.

A numbers studies had been reported that the polymorphisms in the Interleukin 4 (IL-4) and Interleukin 13 (IL-13) genes were associated with susceptibility to asthma. However, the results were inconsistent and inconclusive. We carried out a meta-analysis of case-control genetic association studies to assess whether the combined data showed this association by using a genetic model-free approach. Thirty studies (total 12,781 asthma and 11,500 controls) for the IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A with asthma were included in the meta-analysis. The results indicated that there were an association between the IL-4 C-33T (P = 0.006) and C-589T (P = 0.04), IL-13 C-1112T (P = 0.002) and G+2044A (P = 0.04) and susceptibility to asthma. And the definition of asthma subgroup meta-analysis demonstrates that the IL-4 C-33T is not associated with nonatopic or atopic, and IL-4 C-589T and IL-13 C-1112T polymorphisms are not associated with atopic. In the ethnicity subgroup meta-analysis, the IL-4 -589T (P = 0.003) and the IL-13 -1112T (P < 0.00001) alleles are associated with asthma among Caucasian, but not on the IL-13 +2044A allele. In conclusion, IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A could be proposed as asthma susceptible SNPs. Further investigation in larger studies and meta-analysis is required.

Cytochalasin B treatment of mouse oocytes during intracytoplasmic sperm injection (ICSI) increases embryo survival without impairment of development.

Intracytoplasmic sperm injection (ICSI) is a technique commonly used in clinical and research settings. In mouse oocytes, conventional ICSI has a poor survival rate caused by a high level of lysis. Cytochalasin B (CB) is a toxic microfilament-inhibiting agent that is known to relax the cytoskeleton and enhance the flexibility of oocytes. CB has been used widely in nuclear transfer experiments to improve the success rate of the micromanipulation, however information describing the use of CB in ICSI is limited. Here, we demonstrated that the addition of 5 µg/ml CB to the manipulation medium of ICSI procedure significantly improved the survival rate of the ICSI embryos (80.74% vs. 89.50%, p < 0.05), and that there was no harm for the in vitro or in vivo development. The birth rates and birth weights were not significantly different between the CB-treated and -untreated groups. Interestingly, the microfilaments of the ICSI embryos were almost undetectable immediately after CB treatment; however, they gradually re-appeared and had fully recovered to the normal level 2 h later. Moreover, CB did not disturb spindle rotation, second polar body formation or pronuclei migration, and had no effect on the microtubules. We thus conclude that ICSI manipulation in CB-containing medium results in significantly improved survival rate of mouse ICSI embryos, and that short-term treatment with CB during ICSI manipulation does not have adverse effects on the development of ICSI embryos.

RAD51 G135C polymorphism is associated with breast cancer susceptibility: a meta-analysis involving 22,399 subjects.

Several studies have investigated the associations between RAD51 G135C polymorphism and the susceptibility to breast cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 case control studies, including 12,153 cases and 10,245 controls, were selected. Overall, significant decreased risk was found for the additive model (OR = 0.995, 95% CI = 0.991-0.998) and dominant model (OR = 0.994, 95% CI = 0.991-0.998). In the subgroup analysis by ethnicity, statistically significantly decreased risk was found in Asians (additive model: OR = 0.977, 95% CI = 0.954-1.000 and dominant model: OR = 0.981, 95% CI = 0.963-1.000). In conclusion, this meta-analysis suggests that the RAD51 G135C polymorphism is a low-penetrant risk factor for developing breast cancer.

Icariin induces mouse embryonic stem cell differentiation into beating functional cardiomyocytes.

Icariin, the primary active component of Epimedium extracts, has recently been shown to induce cardiomyocyte differentiation of murine embryonic stem (mES) cells in vitro. However, as these cardiomyocytes were not functionally characterized, the potential application of icariin-induced cardiomyocytes in clinical practice remains unclear. Therefore, in this study, we characterized the structure and function of icariin-induced cardiomyocytes to evaluate their potential application in transplantation for cardiac failure treatment. mES cells were cultured as embryoid bodies (EBs) via the direct suspension method in the presence of icariin. The protein expression profiles and ultrastructural characteristics of mES cell-derived cardiomyocytes were then characterized by immunofluorescence and transmission electron microscopy, respectively. In addition, the expression of cardiac-specific and calcium handling genes was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cardiomyocytes induced by icariin treatment expressed the cardiac-specific proteins myosin light chain-1v (MLC1v), atrial natriuretic polypeptide (ANP), and cardiac troponin I (cTnI). Furthermore, these cells appeared to possess myofibrils organized into mature sarcomeres that had formed A and I bands. In addition, icariin treatment upregulated the mRNA levels of MLC1v, ANP, cTnI, calsequestrin (CSQ), and sodium-calcium exchanger (NCX) in these cells. Icariin induces the differentiation of mES cells into beating cardiomyocytes with normal structure and function. Therefore, these cells may have promising applications in cardiac cell therapy or tissue engineering.

The distribution and expression of claudin-5 and occludin at the rat blood-optic nerve barrier after borneol treatment.

The purpose of this study is to investigate the distribution and expression of the tight junction membrane proteins, claudin-5 and occludin, in rat blood-optic nerve barrier after borneol treatment. Seventy-two female Wistar rats were randomly divided into the borneol gastric lavage group and the equal volume solvent gastric lavage control group. The bilateral optic nerve from the retrobulbar region to the optic chiasma was collected from the rats in the two groups before gastric lavage and at 30 min, 1, 2, 4, and 8 h after gastric lavage. The distribution and expression of claudin-5 and occludin were detected using immunofluorescence staining, Western blotting, and reverse transcription polymerase chain reaction (RT-PCR). Results showed that claudin-5 translocated from the cell membrane to the cytoplasm at 30 min following initiation of borneol treatment, and this translocation peaked at 1 h. During this period of time, a small amount of occludin also translocated from the cell membrane to the cytoplasm. Four hours after initiation of treatment, claudin-5 and occludin levels in the cytoplasm began to decrease and were restored to their normal pattern 8 h after initiation of treatment. There were no significant differences in the levels of claudin-5 or occludin before or after treatment in either group. It was concluded that claudin-5 and occludin translocate within cells of the rat blood-optic nerve barrier after borneol treatment, and this translocation was reversible. Claudin-5 may play a potential role in permeability of the blood-optic nerve barrier following borneol treatment.

RA induces the neural-like cells generated from epigenetic modified NIH/3T3 cells.

Recently, differentiated somatic cells had been reprogrammed to pluripotential state in vitro, and various tissue cells had been elicited from those cells. Epigenetic modifications allow differentiated cells to perpetuate the molecular memory needed for the cells to retain their identity. DNA methylation and histone deacetylation are important patterns involved in epigenetic modification, which take critical roles in regulating DNA expression. In this study, we dedifferentiated NIH/3T3 fibroblasts by 5-aza-2-deoxycytidine (5-aza-dC) and Trichstatin A (TSA) combination, and detected gene expression pattern, DNA methylation level, and differentiation potential of reprogrammed cells. As the results, embryonic marker Sox2, klf4, c-Myc and Oct4 were expressed in reprogrammed NIH/3T3 fibroblasts. Total DNA methylation level was significant decreased after the treatment. Moreover, exposure of the reprogrammed cells to all trans-retinoic acid (RA) medium elicited the generation of neuronal class IIIbeta-tubulin-positive, neuron-specific enolase (NSE)-positive, nestin-positive, and neurofilament light chain (NF-L)-positive neural-like cells.

MSCs guide neurite directional extension and promote oligodendrogenesis in NSCs.

Previous studies have shown that mesenchymal stem cells (MSCs) enhance repair following injury or degenerative diseases in the central nervous system, but the underlying mechanisms remain unclear. The present study investigated the functional relationship between MSCs and neural stem cells (NSCs) using co-culture systems. Results demonstrated that MSCs promoted outgrowth and guided directional extension of NSC-derived neurites. The majority of neurites were oriented parallel along the MSC axis. Stripe assay results indicated that cell adhesion molecule and extracellular matrix, such as N-cadherin, fibronectin, and laminin, contributed to this effect. Furthermore, Western blot analysis revealed that phosphorylation of cAMP response element-binding protein (CREB) increased during this process. In addition, MSCs promoted differentiation of NSCs into oligodendrocytes via secreted soluble factors. The oligodendrocytes were distributed along the MSC surface in a regular pattern. This study demonstrated that MSC transplantation could be a potential strategy for treating central nervous system injuries.

Administration of bone marrow stromal cells ameliorates experimental autoimmune myasthenia gravis by altering the balance of Th1/Th2/Th17/Treg cell subsets through the secretion of TGF-beta.

Bone marrow stromal cells (BMSCs) are strong candidates for cell therapy against human autoimmune diseases. Intravenous administration of syngenic BMSCs to EAMG-model rats effectively ameliorated the disease, partially through a TGF-beta-dependent mechanism. The proliferative ability of T or B cells from EAMG rats was inhibited by BMSCs at proper cocultured ratios. And the imbalance of Th1, Th2, Th17 and Treg cell subsets accompanied with the development of EAMG was corrected by the administration of BMSCs. These results provide further insights into the pathogenesis of MG, EAMG, and other immune-mediated diseases, and support a potential role for BMSCs in their treatment.

Association of ADAM33 gene polymorphisms with adult concomitant allergic rhinitis and asthma in Chinese Han population.

Allergic Rhinitis (AR) and allergic asthma (AS) are very common diseases involving genetic and environmental factors. Most patients with asthma also have rhinitis, which suggests the concept of 'one airway, one disease'. A disintegrin and metalloproteinase 33 (ADAM33) was discovered as the first asthma-susceptible gene by positional cloning. To evaluate the potential influences of ADAM33 gene polymorphisms on concomitant allergic rhinitis and asthma (ARA), a case-control study was conducted in Han population of Northeast China. Six polymorphic sites (V4, T + 1, T2, T1, S1 and Q - 1) were genotyped in 135 ARA patients and 151 controls (CTR). Genotypes were determined by the polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. Data was analyzed using the Chisquaretest and Haploview software. The SNPs (V4 G/C, T2 A/G, T1 G/A, and Q - 1A/G) of the ADAM33 gene may be the causal variants in ARA disease.

TGF-beta expression by allogeneic bone marrow stromal cells ameliorates diabetes in NOD mice through modulating the distribution of CD4+ T cell subsets.

BMSCs could promote the regeneration of islet beta-cell, but the status of BMSCs under diabetes is still unknown. Our study verified the effect of allogeneic BMSCs (ICR) transferred into NOD mice on blood glucose and CD4+ T cells subsets function. In vivo experiment, BMSCs could decrease blood glucose, weaken lymphocytes proliferation. In vitro experiment, the distribution of CD4+ T cell subsets was changed after co-culture with BMSCs, resulting in a greater frequency of Treg cells and reduced representation of Th17 cells. After TGF-beta blockade, CD4+ T cells differentiated along a route favoring development of Th17, but not Treg cells. Thus, NOD can be treated by BMSCs which changes the distribution of CD4+ T cells, increases the number of Treg cells, and inhibits the differentiation of Th17 cells. And the positive effects of allogeneic BMSCs in the treatment of NOD mice depend on the regulation of TGF-beta secreted by BMSCs.

Association of ADAM33 gene polymorphisms with adult allergic asthma and rhinitis in a Chinese Han population.

BACKGROUND: Rhinitis and asthma are very common diseases involving genetic and environmental factors. Most patients with asthma also have rhinitis, which suggests the concept of 'one airway, one disease.' A disintegrin and metalloproteinase 33 (ADAM33) is the first asthma-susceptible gene to be discovered by positional cloning. To evaluate the potential influence of ADAM33 gene polymorphisms on allergic rhinitis (AR) and allergic asthma (AS), a case-control study was conducted on the Han population of northeast China. METHODS: Six polymorphic sites (V4, T+1, T2, T1, S1, and Q-1) were genotyped in 128 patients with AR, 181 patients with AS, and 151 healthy controls (CTR). Genotypes were determined by the polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. Data were analyzed using the chi-square test with Haploview software. RESULTS: The single nucleotide polymorphisms (SNPs), V4 G/C, T+1 A/G, and T1 G/A, of the ADAM33 gene may be the causal variants in AR, whereas ADAM33 V4 G/C, T2 A/G, T1 G/A, and Q-1A/G may participate in the susceptibility of AS. CONCLUSION: These results suggest that polymorphisms of the ADAM33 gene may modify individual susceptibility to AR and AS in a Chinese Han population.

Voriconazole into PLGA nanoparticles: improving agglomeration and antifungal efficacy.

This study is concerned with preparing PLGA nanoparticles loaded with voriconazole (PNLV), investigating the burst release and agglomeration of PNLV, and also evaluating antifungal efficacy of PNLV compared with voriconazole (VRC). The emulsion-solvent evaporation technique for nanoparticles and tests against fungi were completed. The amount of VRC in PNLV with sodium hexametaphosphate was 2.01+/-0.27%, and burst release of PNLV was reduced by about 33% using 20% ethanol solution (n=3). The mean D(50) of PNLV with or without this salt was 132.8 nm and 6.3 microm, respectively (n=5). In vitro; the fungal numbers treated with PNLV (3.5 mg/ml, equal amount calculated by VRC) and VRC (70 microg/ml) in tubes at the day 7 were 5.74 log(10) and 6.72 log(10), respectively (P<0.05). In vivo; the fungal burden treated with PNLV and VRC in tissue from mice kidneys at day 7 after administration was 0.64 log(10) and 2.61 log(10), respectively (5 mg/kg, P<0.001). The hematoxylin-eosin stain in mice kidney showed that the pathological lesions treated with PNLV were relieved in contrast with those with VRC. These results suggest that the emulsion-solvent evaporation process is feasible in preparing PNLV. Moreover, ethanol solution decreased burst release and Na-HMP inhibited agglomeration. PNLV could improve the VRC antifungal efficacy.

Association between hyperpolarization-activated channel in interstitial cells of Cajal and gastrointestinal dysmotility induced by malignant ascites.

Advanced malignant ascites is accompanied by gastrointestinal dysmotility, and patients often feel abdominal pain, abdominal distention, nausea and constipation. Gastrointestinal dysmotility is not only painful for the patients, but it reduces the absorption of nutrients and affects the physical recovery of patients with malignant ascites. It is reported that changes in interstitial cells of Cajal (ICCs) are responsible for the gastrointestinal dysmotility induced by malignant ascites, but the mechanism is not completely understood. The present study observed a significantly decreased expression of ion channels, including hyperpolarization-activated cyclic nucleotide-gated potassium channel 2 (HCN2) and cyclic adenosine monophosphate, in the condition of malignant ascites. Using electrophysiology, it was identified that malignant ascites led to lower amplitude and slower frequency signals in cells of the small intestine. In addition, when ICCs were cultured with malignant ascites in vitro, the expression of HCN2 of ICCs was significantly reduced, and the data of flow cytometry revealed that the Ca2+ concentration of ICCs was also decreased. The results of electron microscopy analysis demonstrated the nuclei of ICCs were pyknotic, and the processes of ICCs were reduced in malignant ascites. The present study suggests the small intestinal dysmotility caused by malignant ascites may be associated with changes in HCN2 of ICCs, which offers a potential therapeutic target for gastrointestinal dysmotility in advanced malignant ascites.

Human neural stem cells promote corticospinal axons regeneration and synapse reformation in injured spinal cord of rats.

BACKGROUND: Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord. METHODS: NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n = 15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group, NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA. RESULTS: NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P < 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P < 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression colocalized with BDA positive axons and neurons distal to the injury site. Transplanted cells were found to migrate into the lesion, but not scatter along the route of axon grows. The cells differentiated into astrocytes or oligodendrocytes, but not into the neurons after transplantation. Furthermore, NSC medium administration did not limit the degree of axon sprouting and functional recovery of the injured rats compared to the NSC graft group. CONCLUSIONS: Human embryonic neural stem cells can promote functional corticospinal axons regeneration and synapse reformation in the injured spinal cord of rats. The action is mainly through the nutritional effect of the stem cells on the spinal cord.