Biomedical subjects

Suming Zhang

Publications and source records attributed to Suming Zhang.

11 recordsLinked to original sources

PubMed2006

Perihematoma damage at different time points in experimental intracerebral hemorrhage.

The damage degree of neurons in perilesion at different time points was observed in order to explore the optimal operation occasion. Piglet lobar hematomas were produced by pressure-controlled infusions of 2.5 mL autonomous blood into the right frontal hemispheric white matter over 15 min, and the metabolic changes were ambulatorily detected with MRS at 3rd, 12th, 24th and 48th h after hematoma induction. Brain tissues of perihematoma were also obtained at different time points. The transcription level of Bax gene was detected by in situ hybridization and apoptosis by TUNEL technique, and the pathologic change of neurons was observed under an electron microscope. The results showed that the number of Bax positive cells reached the peak at 24 h (79.00 +/- 4.243/5 fields). There was no significant difference in A values between 3 h and 6 h, 12 h (P > 0.05), but there significant difference between 24 h and 3 h, 6 h, 12 h (P < 0.05). The number of apoptotic cells reached the peak at 24 h (P < 0.001), and there was no significant difference between 3 h and 6 h (P = 0.999). The area of the apoptotic cells showed no significant difference between 3 h and 6 h or among 3 h, 6 h and 6 h (P > 0.05). Lac peak mainly occurred at 24 h and 48 h, while on the healthy side, no Lac peak was detectable. The ratio of NAA/Cr presented a descent tendency, but there was no significant difference among the groups before 12 h (P > 0.05), there was very significant difference between 3, 6 and 24, 48 h (P < 0.01). Under electronic microscopy, the neuronal damage surrounding hematoma in 3 to 6 h was milder than in 24 h to 48 h. It was concluded that the secondary apoptosis, damage and metabolic disturbance of the neurons surrounding hematoma was milder in 3-6 h in acute intracerebral hemorrhage, while obviously aggravated in 24-48 h. An effective intervention is needed to reduce secondary damage as soon as possible.

Animals↗

PubMed2006

Induction of silencing effect of Swedish mutant amyloid precursor protein by RNA interference.

Over-expression of APP and Swedish mutation could cause some familial early onset AD. In this study, a primary screening was conducted of effective small interference RNAs (siRNAs) targeted wild type APP (APPwt) and Swedish mutant APP (APPswe). One siRNA targeting APPwt and the other siRNA targeting APPswe were designed. All these siRNAs were endogenously expressed by siRNAs expressing plasmids. COS-7 cells were transiently co-transfected with APP-GFP recombinant plasmids and siRNA expression vector. The silencing effect of each siRNA was quantitatively assessed by the level of expression of green fluorescent protein (GFP). It was found that the siRNAs silenced APPwt and APPswe to different degrees. siRNA directed against APPswe was more effective in suppressing the expression of fusion gene of APPswe than that of APPwt. The silencing effect of siRNA directed against APPswe indicating allele-specific silencing property of the siRNAs. Therefore, siRNAs directed against APP play an important role both in the therapeutic study of Alzheimer disease and functional exploration ofAPP gene.

Amyloid beta-Protein Precursor↗

PubMed2006

Differentiation and neurological benefit of the mesenchymal stem cells transplanted into the rat brain following intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is often a fatal event. In a patient who survives the initial ictus, the resulting hematoma within brain parenchyma can trigger a series of events that lead to secondary insults and severe neurological deficits. Great efforts have been focused on searching for new approaches to help patients recover neurological function after ICH. Previous studies indicate that mesenchymal stem cells (MSCs) grafted into the ischemic rat brain can improve neurological function. However, there is no report regarding whether MSCs can be used in the same way to improve the neurological function after ICH. We generated the ICH model by injecting collagenase VII into rat brain. Subsequently, 5-bromo-2-deoxyuridine (BrdU)-labeled mesenchymal stem cells were delivered into the brain through carotid artery, cervical vein or lateral ventricle. The distribution and differentiation of MSCs were investigated by methods of immunohistochemistry. We found that MSCs were able to differentiate into neural cells in vitro as well as in the rat brain after ICH. The injected MSCs were able to migrate into hippocampus, blooding foci and ipsilateral cortex. In the hippocampus, MSCs differentiated into neurons; but in surrounding bleeding foci, they differentiated into neurons and astrocytes. In the ipsilateral cortex, MSCs differentiated into neurons, astrocytes and oligodendrocytes. Notably, the motor function of the rats in the carotid artery (CA) group and the lateral ventricle (LV) group improved significantly. Collectively, our study indicates that MSCs are able to differentiate into neural cells in the rat brain after ICH and can significantly improve motor function.

Animals↗

PubMed2005

Prediction of radiation sensitivity using a gene expression classifier.

The development of a successful radiation sensitivity predictive assay has been a major goal of radiation biology for several decades. We have developed a radiation classifier that predicts the inherent radiosensitivity of tumor cell lines as measured by survival fraction at 2 Gy (SF2), based on gene expression profiles obtained from the literature. Our classifier correctly predicts the SF2 value in 22 of 35 cell lines from the National Cancer Institute panel of 60, a result significantly different from chance (P = 0.0002). In our approach, we treat radiation sensitivity as a continuous variable, significance analysis of microarrays is used for gene selection, and a multivariate linear regression model is used for radiosensitivity prediction. The gene selection step identified three novel genes (RbAp48, RGS19, and R5PIA) of which expression values are correlated with radiation sensitivity. Gene expression was confirmed by quantitative real-time PCR. To biologically validate our classifier, we transfected RbAp48 into three cancer cell lines (HS-578T, MALME-3M, and MDA-MB-231). RbAp48 overexpression induced radiosensitization (1.5- to 2-fold) when compared with mock-transfected cell lines. Furthermore, we show that HS-578T-RbAp48 overexpressors have a higher proportion of cells in G2-M (27% versus 5%), the radiosensitive phase of the cell cycle. Finally, RbAp48 overexpression is correlated with dephosphorylation of Akt, suggesting that RbAp48 may be exerting its effect by antagonizing the Ras pathway. The implications of our findings are significant. We establish that radiation sensitivity can be predicted based on gene expression profiles and we introduce a genomic approach to the identification of novel molecular markers of radiation sensitivity.

Carrier Proteins↗

PubMed2005

The derivation of two additional human embryonic stem cell lines from day 3 embryos with low morphological scores.

BACKGROUND: Immune rejection can lead to the failure of human embryonic stem cell (hES cell) transplantation. One approach to address the problem is to establish hES cell line banks. Due to the limited source of human embryos and to ethical reasons, the hES cell lines are not readily available. This study was undertaken to determine whether discarded day 3 embryos with low morphological scores could develop into blastocysts and produce hES cell lines. METHODS: A total of 130 day 3 embryos with low morphological scores were cultured to blastocyst stage, and inner cell masses (ICM) were isolated by immunosurgery. Colonies derived from the ICM were passaged every 4-7 days and evaluated for cell surface markers, differentiation potentials and karyotypes. RESULTS: A total of 19 blastocysts were obtained from 130 embryos (quality score <16), which resulted in the formation of 10 ICM, and two cell lines. Both cell lines satisfied the criteria that characterize pluripotent hES cells. CONCLUSION: Our results suggest that a subset with poor quality day 3 embryos judged on the basis of morphological assessment can form blastocysts and give rise to hES cell lines.

Blastocyst↗

PubMed2005

An early continuous experimental study on magnetic resonance diffusion-weighted image of focal cerebral ischemia and reperfusion in rats.

The chronological and spatial rules of changes during focal cerebral ischemia and reperfusion in different brain regions with magnetic resonance diffusion-weighted imaging (DWI) in a model of occlusion of middle cerebral artery (MCAO) and the development of cytotoxic edema in acute phase were explored. Fifteen healthy S-D rats with MCA occluded by thread-emboli were randomly divided into three groups. 15 min after the operation, the serial imaging was scanned on DWI for the three groups. The relative mean signal intensity (RMSI) of the frontal lobe, parietal lobe, lateral cauda-putamen, medial cauda-putamen and the volume of regions of hyperintense signal on DWI were calculated. After the last DWI scanning, T2 WI was performed for the three groups. After 15 min ischemia, the rats was presented hyperintense signals on DWI. The regions of hyperintense signal were enlarged with prolonging ischemia time. The regions of hyperintense signal were back to normal after 60 min reperfusion with a small part remaining to show hyperintense signal. The RMSIs of parietal lobe and lateral cauda-putamen were higher than that of the frontal lobe and medial cauda-putamen both in ischemia phase and recanalization phase. The three groups were normal on T2 WI imaging. DWI had good sensitivity to acute cerebral ischemia, which was used to study the chronological and spatial rules of development of early cell edema in ischemia regions.

Animals↗

PubMed2004

Mechanism of in vitro differentiation of bone marrow stromal cells into neuron-like cells.

In order to study whether marrow stromal cells (MSCs) can be induced into nerve-like cells in vitro, and the mechanism, the MSCs in Wistar rats were isolated and cultured, and then induced with DMSO and BHA in vitro. The expression of specific marking proteins in neurons, glia and neural stem cells were detected before preinduction, at 24 h of preinduction, at 6 h, 24 h, and 48 h of neuronal induction by using immunohistochemistry and Western blotting. The ultrastructural changes after the inducement were observed. The results showed that after the inducement, many MSCs turned into bipolar, multipolar and taper, and then intersected as network structure. At the same time, some MSCs had the typical neuron-like ultrastructure. Immunohistochemistry revealed that NeuN and Nestin expression was detectable after inducement, but there was no GFAP and CNP expression. Western blotting showed the expression of Nestin was strong at 6 h of neuronal induction, and decreased at 24 h, 48 h of the induction. NeuN was detectable at 6 h of neuronal induction, and increased at 24 h, 48 h of the induction. It was concluded MSCs were induced into neural stem cells, and then differentiated into neuron-like cells in vitro.

Animals↗

PubMed2004

Experimental study on the expression of HIF-1alpha and its relationship to apoptosis in tissues around cerebral bleeding loci.

The expression of hypoxia inducible factor-1 alpha (HIF-1alpha) and its relationship to apoptosis in tissues around cerebral bleeding loci was studied. The expression of HIF-1alpha and apoptosis in 37 samples of tissues around cerebral bleeding loci and 9 samples of normal cerebral tissues was assessed by immunohistochemical straining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling methods. In 37 tissue samples around cerebral bleeding loci, the positive rate of the HIF-1alpha expression was 40.6%. Especially in the patients with amount of bleeding >60 ml, the positive rate (88.9%) of the HIF-1alpha expression was significantly higher than those with the amount of bleeding ranging from 30-45 ml or 45-60 ml (P<0.05). The expression of HIF-1alpha was increased as the amount of bleeding and operative time increased (P<0.05). There existed a positive correlation between HIF-1alpha labeling index and apoptosis index (n=12, r=0.56, P<0.01). These results suggested that the expression of HIF-1alpha was closely related with the time of hemorrhage and the amount of bleeding, and could induce the apoptosis of neurons.

Adult↗

PubMed2002

Induction of the expression of heme oxygenase gene in PC12 cells by hypoxia.

To investigate the expression of the HO-1 gene in PC12 cells in hypoxic environment and gain further insight to the role of HO-1 in cerebral ischemia, PC12 cells were exposed to hypoxia environment (95% N2, 5% CO2) for 0.5 h, 1 h, 4 h, 8 h, 12 h, 24 h respectively. The level of HO-1 mRNA was examined by reverse transcriptase polymerase chain reaction (RT-PCR); the volume of COHb in the media were measured spectrophotometrically and the cGMP concentration of PC12 cell extracts was determined by radioimmunoassay. We found that after exposure to hypoxia for 1 h, 4 h, 8 h, 12 h, 24 h, HO-1 mRNA increased by 3%, 4%, 17%, 31% 36% as compared with that in control group respectively (P < 0.01 or P < 0.05); the COHb increased by 12%, 29%, 59%, 88%, 94% as compared with that in control group respectively (P < 0.01 or P < 0.05), and the cGMP concentration were 2.2, 3.4, 5.2, 8.1, 10.9-fold as that of the control group (P < 0.01). We are led to conclude that hypoxia induced the expression of HO-1 gene, the production of endogenous CO, and the concentration of cGMP was elevated as well.

Animals↗

PubMed2002

An experimental proton magnetic resonance spectroscopy analysis on early stage of acute focal cerebral ischemia.

Using different models of focal cerebral ischemia, the temporal and spatial rules of metabolism and energy changes in the post-ischemia brain tissue were measured by proton magnetic resonance spectroscopy (1HMRS) to provide valuable information for judging the prognosis of acute focal cerebral ischemia and carrying out effective therapy. Nine healthy Sprague-Dawly rats (both sexes) were randomly divided into two groups: The rats in the group A (n = 4) were occluded with self-thrombus for 1 h; The rats in the group B (n = 5) were occluded with thread-emboli for 1 h. The 1H MRS at 30, 40, 50, 60 min respectively was examined and the metabolic changes of NAA, Cho and Lac in the regions of interest were semiquantitatively analyzed. The spectrum integral calculus area ratio of NAA, Cho, Lac to Pcr + Cr was set as the criterion. The values of NAA.Cho in the regions of interest were declined gradually within 1 h after ischemia, especially, the ratio of Cho/(Pcr + Cr), NAA/(Pcr + Cr) at 60 min had significant difference with that at 50 min (P < 0.05). The ratio of Lac/(Pcr + Cr) began to decrease at 40 min from initial increase of Lac in both A and B groups. MR proton spectrum analysis was a non-invasive, direct and comprehensive tool for the study of cellular metabolism and the status of the biochemical energy in acute ischemia stroke.

Animals↗

PubMed2002

Expression of recombinant adeno-associated virus in the brain of rats with a focal embolic stroke via carotid artery.

OBJECTIVE: To study whether recombinant adeno-associated virus (rAAV) mediated foreign gene, LacZ, could pass the blood brain barrier by intra-carotid artery delivery and express in vivo in ischemic brain of the focal embolic stroke rats to investigate a possibility of delivering foreign gene through carotid artery to treat acute ischemic stroke. METHODS: The carotid artery territory in 41 rats was embolized with or without arterial-like fibrin rich clots to make a model of focal embolic stroke rat. rAAV containing LacZ gene (rAAV-LacZ) was constructed in 293 cells by calcium phosphate cotransfection. The rats were assigned to one of the following treatments: 1 control (without embolism) groups, including PBS treated (n = 6), pLacZ treated (n = 6 ) and rAAV-LacZ treated (n = 6): 2 embolic groups, including embolism + PBS (n =7),embolism + pLacZ (n = 8) and embolism + rAAV-LacZ (n = 8). Brains were cryosectioned and kappa-Gal stain was performed at 2, 4, and 8 weeks, respectively, after transfection, and then infarct volume was measured and the percentage of LacZ staining-positive cells was calculated. RESULTS: In all the control groups and embolism + PBS treated animal, no kappa-Gal staining-positive cells were found, but in embolism + pLacZ (n = 8) and embolism+rAAV-LacZ groups a lot of kappa-Gal staining-positive cells were found. The expression cells were in the tissues around the infarction. The gene expression persisted only nearly four weeks in embolic group with pLacZ. In the embolic group with rAAV-LacZ the expression was very stable during the experiment course (eight weeks) and the percentage of the expressed cells was significantly higher than that of its contralateral areas at the same time points, respectively. CONCLUSIONS: The plasmid vector and rAAV could enter the brain through the ischemia-damaged blood barrier and foreign gene can be expressed in brain. The positive gene expression is mainly in the peripheral areas of the infarction. rAAV as a permanent expression vector may ultimately be used for gene therapy of human ischemia cerebravascular diseases.

Animals↗