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Yi Li

Publications and source records attributed to Yi Li.

At least 163 records · Page 9Linked to original sources
PubMed2005

Effective algorithms for tag SNP selection.

Single nucleotide polymorphisms (SNPs), due to their abundance and low mutation rate, are very useful genetic markers for genetic association studies. However, the current genotyping technology cannot afford to genotype all common SNPs in all the genes. By making use of linkage disequilibrium, we can reduce the experiment cost by genotyping a subset of SNPs, called Tag SNPs, which have a strong association with the ungenotyped SNPs, while are as independent from each other as possible. The problem of selecting Tag SNPs is NP-complete; when there are large number of SNPs, in order to avoid extremely long computational time, most of the existing Tag SNP selection methods first partition the SNPs into blocks based on certain block definitions, then Tag SNPs are selected in each block by brute-force search. The size of the Tag SNP set obtained in this way may usually be reduced further due to the inter-dependency among blocks. This paper proposes two algorithms, TSSA and TSSD, to tackle the block-independent Tag SNP selection problem. TSSA is based on A* search algorithm, and TSSD is a heuristic algorithm. Experiments show that TSSA can find the optimal solutions for medium-sized problems in reasonable time, while TSSD can handle very large problems and report approximate solutions very close to the optimal ones.

Algorithms↗
PubMed2005

mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma.

Combined activation of Ras and AKT leads to the formation of astrocytic glioblastoma multiforme (GBM) in mice. In human GBMs, AKT is not mutated but is activated in approximately 70% of these tumors, in association with loss of PTEN and/or activation of receptor tyrosine kinases. Mechanistic justification for the therapeutic blockade of targets downstream of AKT, such as mTOR, in these cancers requires demonstration that the oncogenic effect of PTEN loss is through elevated AKT activity. We demonstrate here that loss of Pten is similar to AKT activation in the context of glioma formation in mice. We further delineate the role of mTOR activity downstream of AKT in the maintenance of AKT+KRas-induced GBMs. Blockade of mTOR results in regional apoptosis in these tumors and conversion in the character of surviving tumor cells from astrocytoma to oligodendroglioma. These data suggest that mTOR activity is required for the survival of some cells within these GBMs, and mTOR appears required for the maintenance of astrocytic character in the surviving cells. Furthermore, our study provides the first example of conversion between two distinct tumor types usually thought of as belonging to specific lineages, and provides evidence for signal transduction-mediated transdifferentiation between glioma subtypes.

Animals↗
PubMed2005

Human marrow stromal cells enhance connexin43 gap junction intercellular communication in cultured astrocytes.

Human marrow stromal cells (hMSCs) provide functional benefit in rats subjected to stroke. Astrocytes are coupled into a cellular network via gap junction channels, predominantly composed of connexin-43 (Cx43) proteins. Astrocytes are believed to play a vital role in neuroprotection by providing energy substrates to neurons and by regulating the concentrations of K+ and neurotransmitters via gap junctions. We therefore investigated the effect of factors secreted by hMSCs on gap junction intercellular communication (GJIC), expression of Cx43, and phosphorylation of Cx43 in an astrocyte cell culture system. Exposing rat cortical astrocytes to various concentrations of hMSC conditioned medium, we demonstrate that hMSCs produce soluble factors that significantly increase astrocytic GJIC, measured by the scrape-loading dye transfer method. Immunohistochemistry and Western blot showed increased Cx43 expression concomitant with altered GJIC. As the PI3K/Akt signaling pathway has been demonstrated to alter gap junction expression and GJIC, we selectively blocked phosphoinositide 3-kinase (PI3K). Addition of the PI3K inhibitor LY294002 decreased GJIC and Cx43 expression in astrocytes. These inhibitory effects of LY294002 were countered by the addition of hMSC conditioned media. Furthermore, coculturing hMSCs with rat astrocytes increased astrocyte GJIC in a manner dependent upon the hMSC/astrocyte ratio. These findings demonstrate that hMSCs secrete soluble factors that increase GJIC of astrocytes through upregulation of Cx43, and indicate a mechanistic role for PI3K.

Animals↗
PubMed2005

[The sequence polymorphism of Y-chromosome DNA and mtDNA of Dong Ethnic of Congjiang, Guizhou].

To study the patrilineal and matrilineal genetic structure and the origin of Dong Ethnic of Congjiang Guizhou. Study the distribution of Y-chromosome haplotypes which consisted of 10 SNPs of Y-DNA and mtDNA haplogroups consisted of 11 SNPs by using PCR-RFLP method. The result is three haplotypes H6,H11,H14 were detected, the frequency of H11 is 92.5%. Six haplogroups were identified by mtDNA analysis, 75% of the people can be identified. The patrilineal genetic structure of Dong of Guizhou is simple, Principle component indicated that the structure is closer to Zhuang-Dong branch of Sino-Tibetan language family. The matrilineal genetic structure of Dong of Guizhou is complicated.

Asian People↗
PubMed2005

[G6PD Gene Mutations in Shui people in Sandu of Guizhou].

UNLABELLED: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. To date, about 126 mutations in the G6PD gene have been detected, among which 17 mutations were found in Chinese. The most common mutations are: 1376 G-->T and 1388 G-->A, both in exon 12; 95 A-->G in exon 2, which amounted to more than 50% of mutations representing various regions and ethnic groups in China. A large-scale screening and genotypic analysis was held in Shui people in Sandu of Guizhou. To investigate the incidence and the molecular basis of G6PD deficiency of Guizhou Shui people, NBT qualitative and G6PD/6PGD quantitative methods were used to detect G6PD deficiency in 1,090 Shui people from the general people belonging to Sandu of Guizhou. By means of mis-matched primers amplified the G6PD gene, the products were 234 bp, 280 bp and 345 bp in length, then restriction enzyme analysis was used to detect the most common Chinese G6PD mutations, 1376 G-->T, 1388 G-->A and 95 A-->G. The results showed that out of the 1,090 samples, 98 G6PD deficiency samples were found. The incidence of G6PD deficiency was 8.99%. 24 cases of 1376 G-->T, 12 cases of 1388 G-->A, 9 cases of 95 A-->G were detected. A sample with 1376 G-->T and 95 A-->G mutation was found in a girl. It was reported for the first time. IN CONCLUSION: 1376 G-->T, 1388 G-->A, 95 A-->G mutations are the common G6PD mutations in Shui people in Sandu of Guizhou. The results indicates that different national minorities of Chinese may originated from a common ancestor.

China↗
PubMed2005

[5, 10-methylenetetrahydrofolate reductase polymorphism in three nationalities of Guizhou in China].

OBJECTIVE: To study the genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) among the Han, Buyi and Miao populations in Guizhou and to provide genetic data for establishment of the genetic polymorphism bank of Guizhou Minorities. METHODS: The technique of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequencies at two mononucleotide sites (677 and 1298) of MTHFR among the Han population in Libo county, the Buyi population in Libo county and the Miao population in Leishan county. RESULTS: At the site of 677, the T allele frequencies were found to be 22.8%, 16.1%, 10.6%, for the Han, Buyi, Miao populations respectively. At the site of 1298, the C allele frequencies were 28.9%, 39.1%, 48.7% for the Han, Buyi, Miao populations respectively. The frequencies for the combined heterozygote of 677CT/1298AC were 16.66%, 22.7%, 11.1% for the three populations respectively. Moreover, one case with combined homozygote of 677TT/1298CC was seen in the Miao population. CONCLUSION: The polymorphisms of the two mononucleotide sites (677 and 1298) of MTHFR are diverse in different populations. The C allele frequencies at the site of MTHFR 1298 of the Miao population in Leishan county and the Buyi population in Libo county are high, and the C allele frequency in the Miao population is higher than those hitherto reported in literature.

Base Sequence↗
PubMed2005

[Genotyping of major outer membrane protein gene of Chlamydia trachomatis by cleavase fragment length polymorphism analysis].

OBJECTIVE: To establish a methed of cleavage fragment length polymorphism (CFLP) analysis with a primer labeled at the 5'-end with digoxigenin for genotyping of Chlamydia trachomatis (Ct). The methods for detection of Ct by major outer membrane protein (MOMP) gene (ompl) with nested polymerase chain reaction (ompl-nPCR) were studied. The incidence of Ct infection in pregnant women, the common genotypes and vertical transmission rate of Ct in Chongqing area during the past one year was also investigated. METHODS: The samples were taken from cervical scrapes of parturient women and nasopharygeal swabs of their neonates from April 2003 to Feb. 2004 in Chongqing Women and Children's Health Care Institute. Totally 300 pairs (605 specimens) were detected by using ompl-nPCR, ompl-PCR (inside pair of primers was used directly) and plasmid-PCR. The results were judged by the modified gold standard (MGS). The ompl-nPCR amplified DNA was purified by recovery of DNA from agarose gel electroelution into dialysis bags. The DNA amplified from ompl-nPCR was sequenced by ABI PRISM 377 DNA sequencer. CFLP assay with a primer labeled at the 5'-end with digoxigenin was created for genotyping of Ct, and was primarily applied. RESULTS: The minimum detectable levels of ompl-nPCR and ompl-PCR corresponded to 2.5 elementary body (EB) and 25 EB, respectively. The sensitivity of ompl-nPCR was 10 times that of ompl-PCR. The positive rate of Ct in the samples from the pregnant women was 11% (33/300). The vertical transmission rate of Ct from mothers to their infants was 24.2% (8/33). The rate of Ct isolated from nasopharyngeal swabs 5 - 10 days after birth was 38.9% (7/18), which was significantly greater than that [3.0% (1/33)] detected within 24 hours after birth (chi(c)(2) = 8.79, P < 0.01). Of the 33 Ct-positive samples from pregnant women, 9 had vaginal delivery and 24 had caesarean section. The vertical transmission rates in vaginal delivery group and caesarean section group were 66.7% (6/9) and 8.3% (2/24), respectively (chi(c)(2) = 9.16, P < 0.01). Incidence of premature rupture of membrane in Ct-positive group was 30.3% (10/33), which was greater than that of Ct-negative groups (13.5%, 36/267, chi(2) = 6.40, P < 0.05). Four different patterns were observed in the 16 Ct-positive samples from 8 pregnant women and 8 matched maternal-infants by using CFLP, which were confirmed by DNA sequencing later. They were type E (3 pairs), type F (2 pairs), type H (2 pairs) and type D (1 pair). Each pair of matched maternal-infantile samples presented identical CFLP pattern. CONCLUSIONS: This study revealed the infection rate of Ct in pregnant women, vertical transmission rate of Ct and the common genotypes of Ct in Chongqing Women and Children's Health Care Institute. The CFLP assay by using a primer labeled at the 5'-end with digoxigenin was first used for genotyping of Ct. The assay showed a good sensitivity and reproducibility, no radioactive contamination, and is simple. Therefore the assay is a potential new method for Ct genotyping.

Cervix Uteri↗
PubMed2005

[Cloning and sequence analysis of recombinant fusion gene of Escherichia coli heat-liable enterotoxin B subunit and Actinobacillus actinomycetemcomitans fimbria associative protein].

OBJECTIVE: To clone the recombinant fusion gene of Escherichia coli heat-liable enterotoxin B subunit (Ltb) and Actinobacillus actinomycetemcomitans fimbria associative protein (Fap). METHODS: Two couples of primers were designed for PCR according to the known sequence of ltb and fap. The ltb and fap gene were obtained by amplification PCR technique from plasmid EWD299 of Escherichia coli and Actinobacillus actinomycetemcomitans 310 DNA respectively, and fused them by PCR. The fusion gene ltb-fap were cloning into plasmid pET28a(+). The recombined plasmid pET28a ltb-fap was transformed into Escherichia coli DH5alpha. The recombinant was screened and identified by restriction enzyme and PCR. The cloned gene was sequenced. RESULTS: The ltb-fap about 531bp in size was obtained successfully, and identified by PCR, restrictive enzyme and sequence analysis. CONCLUSION: The vector of pET28a ltb-fap was obtained.

Aggregatibacter actinomycetemcomitans↗
PubMed2005

[Cloning and expression of a novel gene restin and preparation of antisera against the recombinant restin].

AIM: To clone a new human gene, restin, from retinoic acid-treated promyelocytic cell line HL-60, express the protein in E.coli and prepare the antisera against the protein. METHODS: The restin gene was amplified from retinoic acid-treated promyelocytic cell line HL-60 by RT-PCR and cloned into a prokaryotic expression vector. The recombinant restin was induced to express in E. coli by temperature. After preliminary purification by SDS-PAGE, the restin protein was used to immunize rabbits to obtain antisera. The titers and specificity of the rabbit anti-restin antisera were tested by Western blot and immunofluorescence analysis. RESULTS: Recombinant restin with M(r) being about 26,000 was highly expressed in E. coli. The titers of the anti-sera to restin ranged from 1:100 to 1:800. Immunofluorescence analysis showed that restin distributed mainly in the nuclei of COS-7 cells. CONCLUSION: We successfully prepared the antisera against restin, which are useful for further investigation of biological functions of restin.

Animals↗
PubMed2005

[Effect of ERK1/2 on low shear stress-induced expression of IL-8 mRNA in human endothelial cells].

Fluid shear stress plays an important role in many physiological and pathophysiological processes of the cardiovascular system. It modulates vascular function and structure via stimulating mechanosensitive endothelial cell signal events. Previous studies have identified that the exposure of vascular endothelial cells to fluid mechanical forces can modulate the expressions of many genes, including IL-8 gene. In order to gain an insight into the role of extracellular signal regulated kinase (ERK1/2) signal pathway in the expression of IL-8 mRNA in human umbilical vein endothelial cells (HUVECs) under the stimulation by low shear stress (4.20 dyne/cm2), we employed Western blot to measure phosphorylation of ERK1/2 and used quantitative reversal transcription-polymerase chain reaction (qRT-PCR) to assay the expression of IL-8 mRNA. The results showed: (1) Shear stress could activate ERK1/2 with a rapid, biphasic time course (maximum by 10 min and basal by 2 h); the treatment of HUVECs with Genistein (a highly specific inhibitor of tyrosine protein kinase, TPK) or PD98059 (the inhibitor of mitogen-activated protein/extracellular signal regulated kinase kinase, MEK) culd prevent shear-dependent activation of ERK1/2; (2) When treated with Genistein or PD98059, significant inhibition of IL-8 mRNA expression induced by low shear stress was observed in HUVECs. This in vitro study demonstrates that ERK1/2 plays an important role in IL-8 mRNA expression induced by low shear stress.

Cells, Cultured↗
PubMed2005

[Coronary intervention in 1148 patients with chronic total coronary occlusion].

OBJECTIVE: To assess the technique and outcomes of coronary intervention treatment for patients with chronic total occlusion (CTO) lesions. METHODS: Retrospectively analyzed the data from 1148 patients with CTO who were treated by percutaneous coronary intervention (PCI) between June 1993 and December 2004. There were 1494 CTO lesions in 1458 vessels with a mean occlusion time of (49.1 +/- 31.6) months. A total of 1499 stents were implanted to those target lesions. RESULTS: Total success rates of patients and lesions were 90.2% (1036/1148) and 88.2% (1317/1494), respectively. The success rate of PCI was declined in CTO lesions with long occlusion time, stump missing, bridging collaterals and >or= 15 mm in length (P < 0.05). Operative failures were occurred in 112 patients. Guide wire and balloon failed to pass through the occlusion accounted for 82.1% and 17.9% of all failures respectively. No death was occurred during operation, but 2 patients suffered from acute stent thrombosis and other 9 patients suffered from acute or later pericardium perforation. After procedure, there were 3 patients died and 3 patients suffered from subacute stent thrombosis during in-hospital period. The total in-hospital major adverse cardiac events rate was 0.6% (7/1148). The angina-free survival rate was 87.1% at discharge. CONCLUSION: In an experienced heart center, it is possible to obtain a relatively high success rate of PCI and ideal clinical outcomes in patients with CTO coronary lesions.

Adult↗
PubMed2005

[Soil evaporation under perforated plastic mulch].

In arid and semiarid regions of northwestern China, where evaporation exceeds precipitation, perforated plastic mulches are widely used to decrease soil water evaporation. To determine the effects of various perforated plastic mulches on soil water evaporation after irrigation, a soil column experiment was conducted, which consisted of six mulches with different perforated rates and four levels of irrigation, and the soil water evaporation from each soil column was measured. The results showed that with 100% perforated mulch, the cumulative evaporation was 2.8-48.5 times higher than that of the control, and increased with increasing irrigation amount. There was a linear relationship between cumulative evaporation and time, which followed the Gardner's theory of bare soil evaporation. A three-factor (evaporation time, perforated rate and irrigation amount) function of cumulative evaporation and the functions of relative cumulative evaporation and cumulative evaporation per unit hole area film were established, which fitted the observed data very well.

Crops, Agricultural↗
PubMed2005

[Inhibitory effect of lidamycin on growth of colon carcinoma 26 and hepatic metastasis in mice].

BACKGROUND & OBJECTIVE: Lidamycin (LDM, C-1027), an antitumor antibiotic containing a chromophore of enediyne structure, shows markedly cytotoxicities against cancer in vitro and in vivo. This study was to explore inhibitory effect of LDM on orthotopic transplanted tumors and hepatic metastasis of colon carcinoma 26 (C26) in mice. METHODS: A series of mice C26 models, including subcutaneous transplantation, orthotopic transplantation in cecum subserosa, intra-hepatic transplantation, and hepatic metastases after intra-splenic transplantation, were prepared and received intravenous injection of LDM 72 h after transplantation. Inhibitory rates of tumor growth and hepatic metastasis were calculated. LEICA QWINV3 image analysis system was used to determine the area of metastatic lesions in histopathologic sections. RESULTS: LDM at 0.025, 0.05, and 0.1 mg/kg inhibited the growth of subcutaneous tumors by 64.8%, 78.2%, and 94.2%, orthotopic tumors by 57.5%, 71.5%, and 93.0%, intra-hepatic tumors by 74.5%, 82.3%, and 92.8%, and intra-splenic tumors by 9.2%, 25.8%, and 70.2%, respectively. Determined by the numbers of metastatic nodules, LDM at 0.025, 0.05, and 0.1 mg/kg inhibited hepatic metastases from intra-splenic transplantation by 34.6%, 50.7%, and 76.3%, and larger metastatic lesions (> 2 mm) by 56.6%, 56.7%, and 90.8%, respectively. Evaluated by image analysis of metastatic lesions, LDM at 0.1 mg/kg inhibited hepatic metastases by 71.2%. CONCLUSION: LDM can inhibit growths of subcutaneous, orthotopic, and intra-hepatic transplanted tumors and hepatic metastases of murine colon carcinoma 26.

Aminoglycosides↗
PubMed2005

[Screening susceptibility genes of type 2 diabetes in Chinese population by single nucleotide polymorphism analysis].

OBJECTIVE: To search for the susceptibility variant (s) of type 2 diabetes in the susceptible regions on chr.1 (1p36.23-36.33, 1q24.3-25.1, and 1q42.12-42.13) by genotyping SNP markers in case-control DNA samples and identifying the haplotype associated with type 2 diabetes. METHODS: Totally 124 SNPs in 33 candidate genes in the mapped regions were chosen from public SNP data or identified by sequencing the samples that were used to search for SNP locus. Sequencing method was used to genotype the loci for 236 sporadic type 2 diabetes patients and 152 normal subjects in Northern Han Chinese population. The haplotypes with significant difference were further analyzed. RESULTS: Of 124 SNPs successfully typed, 4 SNPs that showed association with diabetes status were found: rs203849 (P=0.005, OR=1.60) and rs203826 (P=0.016, OR=1.60) located in sAC gene, rs7535528 (P=0.028, OR=1.45) located in PANK4, rs884363 (P=0.043, OR=1.37) located in CASP9 gene. In addition, the frequencies of two combination types from these 4 SNP genotypes were significantly different between case and control groups (P < 0.001). Furthermore, four haplotypes associated with diabetes were found in haplotype analysis of sAC gene. CONCLUSION: sAC, PANK4, and CA SP9 may be associated with type 2 diabetes in Han population in north China, and it seems that the synergetic effect of these genes is responsible for the development of type 2 diabetes.

Adult↗
PubMed2005

[Alteration and potential role of soluble fms-like tyrosine kinase receptor 1 in preeclampsia].

OBJECTIVE: To investigate the alteration of serum soluble fms-like tyrosine kinase receptor 1 (sFlt-1) and the possible source in preeclampsia, and the relationship between sFlt-1 and the pathogenesis of preeclampsia. METHODS: (1) Semi-quantitative RT-PCR was carried out to detect the level of sFlt-1 mRNA in placental tissue of 10 preeclampsia (preeclampsia group) and 10 normotensive pregnancies (normotensive pregnancy group). (2) Enzyme linked immunosorbent assay (ELISA) was used to detect the serum level of sFlt-1 in peripheral venous blood in preeclampsia group 1 (n = 35) and normotensive pregnancies group 1 (n = 35); the serum level of sFlt-1 of uterine vein blood in preeclampsia group 2 (n = 20) and normotensive pregnancies group 2 (n = 20); and the volume of peripheral venous blood sFlt-1 in 10 early (early pregnancy group) and 10 middle pregnancies (middle pregnancy group). RESULTS: (1) sFlt-1 mRNA of placental tissue was significantly higher in preeclampsia group (0.95 +/- 0.04) than that in normal pregnancy group (0.64 +/- 0.15). (2) The serum level of sFlt-1 of peripheral vein in preeclampsia group 1 (5640 +/- 3191) ng/L was higher than that in normal pregnancy group 1 (2194 +/- 635) ng/L. (3) The serum sFlt-1 of uterine vein in preeclampsia group 2 (7673 +/- 2296) ng/L was higher than that in normotensive pregnancy group 2 (3057 +/- 785) ng/L, indicating that the volume of sFlt-1 of uterine vein blood was significantly higher than that of peripheral venous blood (P < 0.01). (4) The serum levels of sFlt-1 in early and middle pregnancy groups were (32 +/- 20) ng/L and (994 +/- 302) ng/L, respectively, showing that the level of sFlt-1 in peripheral venous blood increasingly elevated with the development of pregnancy. CONCLUSIONS: (1) The placenta may be the major source of elevated sFlt-1. (2) The serum level of sFlt-1 is related with the development of pregnancy. The alteration of sFlt-1 may contribute to the pathogenesis of preeclampsia.

Enzyme-Linked Immunosorbent Assay↗
PubMed2005

[Effects of cilostazol on long-term clinical outcomes after coronary stenting].

OBJECTIVE: To evaluate the effects of cilostazol on long-term clinical outcomes in patients underwent coronary stent implantation. METHODS: One hundred patients who underwent coronary stenting were randomly assigned to receive cilostazol 200 mg/d for 6 months (n = 50) or ticlopidine 500 mg/d for 1 month (n = 50). Aspirin 100 mg/d was administrated concomitantly with cilostazol or ticlopidine. Angiographic follow-up was carried out at 6 months and clinical follow-up for 3 years after stenting. RESULTS: Angiographic restenosis occurred in 5 of 34 patients (14.7%) in cilostazol group and 10 of 37 patients (27.0%) in ticlopidine group (P = 0.204). At the end of three-year follow-up, the incidence of major adverse cardiac and cerebral events (MACCE) was greatly reduced in cilostazol group compared with ticlopidine group (16% vs 36%, P = 0.023). Changes of Seattle angina questionnaire (SAQ) physical limitation score showed no significant difference between two groups (21.8 +/- 12.3 vs 16.8 +/- 15.9, P = 0.086). However, changes the improvement of angina frequency score much more was significant in cilostazol group (22.6 +/- 12.7) compared with that in ticlopidine group (16.1 +/- 13.3, P = 0.015). Recurrent angina occurred in 38% of patients in cilostazol group and 54% in ticlopidine group, respectively (P = 0.105). Readmission due to cardiac and cerebral vascular diseases was much less in cilostazol group than that in ticlopidine group (20% vs 40%, P = 0.029). CONCLUSIONS: Cilostazol treatment significantly reduced MACCE and improved the quality of life pf patients in three-year clinical follow-up after coronary stenting.

Adult↗
PubMed2004

Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells.

Human bone marrow stromal cells (hMSCs) enhance neurological recovery after stroke in rodents, possibly via induction of growth factors. We therefore elected to test the effects of hMSC treatment on insulin-like growth factor 1 (IGF-1), which plays an important role in growth, development, neuroprotection and repair in the adult. Rats (n=57) were subjected to permanent middle cerebral artery occlusion (MCAo) and injected intravenously with 3 x 10(6) hMSCs or phosphate-buffered saline (PBS) at 1 day after MCAo. Functional outcome was measured after MCAo using a modified Neurological Severity Score (mNSS). Gene expression of IGF-1 and IGF-1 receptor (IGF-1R) in the ischemic brain tissue were measured at 2 and 7 days after MCAo using reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed to measure the expression of bromodeoxyuridine (BrdU), doublecortin (DCX), IGF-1 and IGF-1R at 7, 14 and 30 days after MCAo. Treatment of MCAo with hMSCs significantly improved functional recovery from 14 to 30 days. MAB1281-labeled hMSCs entered the ischemic brain and increased time-dependently. hMSC treatment significantly increased IGF-1 mRNA and BrdU(+), DCX(+), IGF-1(+) and IGF-1R(+) cells compared to PBS-treated rats (p<0.05). The percentage of BrdU(+) or DCX(+) cells colocalized with IGF-1 increased in the hMSC-treated rats compared to the PBS-treated rats (p<0.05). IGF-1 and IGF-1R may contribute to improved functional recovery and increased neurogenesis after treatment of stroke with hMSCs.

Animals↗