Biomedical subjects

He Wang

Publications and source records attributed to He Wang.

At least 73 records · Page 4Linked to original sources

PubMed2004

Impaired angiogenesis in SHR is associated with decreased KDR and MT1-MMP expression.

This study examined whether retarded angiogenesis in a hypertension animal model was associated with impaired VEGF signaling. Furthermore, we sought to determine whether this impairment could be overcome by VEGF addition. Using a rat sponge implantation model, we confirmed impaired angiogenesis in spontaneous hypertensive rats (SHRs). Fourteen days after sponge implantation, the level of angiogenesis in SHRs was approximately half of those in age-matched normotensive Wistar-Kyoto or Sprague-Dawley rats. Significantly, expression of kinase-insert domain-containing receptor (KDR) and membrane type 1 matrix metalloproteinase (MT1-MMP) was reduced in SHRs compared to controls. Immunohistological analysis indicated endothelial proliferation was decreased in SHRs. Gene transfer of human VEGF(121) increased KDR and MT1-MMP expression in SHRs. VEGF(121) also up-regulated endothelial proliferation and angiogenesis. Our results indicate down-regulated KDR and MT1-MMP expression is associated with an impaired angiogenesis in SHRs. VEGF gene transfer is effective in ameliorating the impaired angiogenesis in SHRs.

Adenoviridae↗

PubMed2004

A novel conditionally replicative adenovirus vector targeting telomerase-positive tumor cells.

PURPOSE: To develop a novel conditionally replicative adenovirus vector that targets telomerase-positive cancer cells. EXPERIMENTAL DESIGN: A telomerase gene-derived promoter was used to control the expression of the E1a gene so that the E1a gene is only expressed in telomerase-positive tumor cells. In addition, a reporter gene was also engineered into the vector so that its infection and replication can be monitored easily. RESULTS: A novel recombinant adenovirus vector that could selectively replicate in telomerase-positive cancer cells was made successfully. This vector showed active replication in a panel of cancer cells and minimal replication in normal human fibroblast or epithelial cells. The recombinant vector could effectively lyse various cultured tumor cells even at very low multiplicity of infection. The replication efficiency in tumor cells is over 10(3)-fold more than normal fibroblast and epithelial cells. In s.c. tumor models, the newly developed telomerase-selective adenovirus vectors exhibited significantly more virus replication and reporter gene expression. CONCLUSIONS: The telomerase-targeted adenovirus vector has significant potential as an oncolytic virus as well as a tumor-specific therapeutic gene delivery vehicle.

Adenoviridae↗

PubMed2004

Dose-dependent neovascularization-promoting effect of adenovirus vector CI-1023 in a rat hindlimb ischaemic model.

CI-1023 (AdGVVEGF121.10) is a replication-deficient adenovirus vector (complete E1a-, partial E1b-, partial E3-) delivering human vascular endothelial growth factor-121 gene. Previous studies from this group have established that CI-1023 can successfully transfer human vascular endothelial growth factor-121 gene resulting in local tissue expression of vascular endothelial growth factor protein. The purpose of this study was to evaluate neovascularization-promoting potency and efficacy of CI-1023 in a wide dose range. In a rat hindlimb ischaemic model, we measured neovascularization-promoting effect of CI-1023 using three end-points: post mortem angiography, immuno-histochemistry and Laser Doppler scanning of tissue blood perfusion. Neovascularization-promoting activity of CI-1023 over the dose range of 4 x 10(6) pu-4 x 10(10) pu was evaluated. Our data demonstrated an obvious dose-dependent effect between 4 x 10(6) pu-4 x 10(8) pu. The neovascularizing effect is somewhat plateaued at the levels between 4 x 10(8) pu and 4 x 10(10) pu. We conclude CI-1023 is a potent neovascularization-promoting compound, with a dose-dependent effect between 4 x 10(6) pu-4 x 10(8) pu in the rat hindlimb ischaemic model.

Angiogenic Proteins↗

PubMed2004

Delayed angiogenesis in aging rats and therapeutic effect of adenoviral gene transfer of VEGF.

We have studied an age-related impairment in angiogenesis and evaluated the effect of overexpressing VEGF in this situation. Polyvinyl alcohol sponges were implanted subcutaneously into aged (24-month), adult (12-month), and young (2-month) rats. Blood vessel ingrowth and proliferative activity in the sponges were assessed by histology with immunostaining for von Willebrand's factor and proliferating cell nuclear antigen (PCNA), respectively. The percentage of total sponge area filled with ingrowing fibrovascular tissue was minimal in aged rats, intermediate in adult rats and highest in young rats. A similar pattern was observed for the total blood vessel numbers in the sponges from old to young animals. The percentage of total sponge endothelial cells (ECs) showing proliferative activity (PCNA positive) was lowest in the aged animals, intermediate in the adult rats and highest in the young rats. To further explore the mechanism of impaired angiogenesis in aged animals, we investigated and found a reduced level of endogenous VEGF protein expression in 12-month-old rats compared to that in 2-month-old rats. VEGF121 gene transfer significantly enhanced blood vessel and fibrovascular tissue ingrowth in adult/aged rats. Adenoviral-VEGF gene transfer also significantly stimulated EC proliferation in aged and adult rats. However, identical treatment failed to further stimulate the already more robust angiogenesis in young animals. The different angiogenic response in adult vs. young rats was not due to differences in gene transfer efficiency, since similar levels of human VEGF121 protein was detected in adult and young rats. Our results indicate that the decreased angiogenic response with aging is associated with reduced EC proliferation and reduced endogenous VEGF production. Adenoviral-VEGF121 gene transfer is effective in augmenting angiogenesis, particularly in older animals.

Adenoviridae↗

PubMed2004

[Experimental study on brain-computer interface based on visual evoked potentials].

Brain-computer interface is a novel EEG-based communication and control system between human brain and computer or some other electric device, which has found important applications in many fields such as rehabilitation engineering. Study has been done in brain-computer interface using visual evoked potentials(VEP). Multiple stimulation patterns were produced on the computer screen through programming. Several flickering blocks were adopted for representing a number of possible selections, and when the subject was fixing his(her) eyes on an object on the screen, the very object could be distinguished by the analysis of the VEPs. Surface electrodes were placed at Oz of the inion and Cz to collect VEP. The wavelet filter and averaging method was used to extract VEP signal. Off-line experimental data analysis indicated that the proposed method may be valuable for developing real brain-computer interface with relatively high accuracy and speed, and the information transfer rates could be higher than 30 bit/min when 12 selections were on the screen.

Brain↗

PubMed2004

Expression and significance of Rap1A in testes of azoospermic subjects.

AIM: To evaluate the Rap1A mRNA expression and its significance in the testes of normal and azoospermic subjects. METHODS: A cDNA microarray that contained Rap1A and some other genes such as RBM, EIF1AY was used to identify the differential gene expression profiles between the normal and azoospermic testes. cDNA probes were prepared by labeling mRNA from azoospermic and normal testicular tissues through reverse transcription with Cy5-dUTP and Cy3-dUTP, respectively. The mixed cDNA probes were then hybridized with cDNA microarray (each containing 4096 unique human cDNA sequences). The fluorescent signals were scanned and the values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated. In situ hybridization was employed to detect the expression of Rap1A in the testes of 10 fertile and 39 azoospermic subjects. RESULTS: One hundred and twenty-eight differentially expressed genes were found to be possibly related to azoospermia, of which 56 were up-regulated and 72, down-regulated genes. The mRNA expression of Rap1A in the spermatogenic cells of azoospermic was stronger than that in those of the fertile testes. CONCLUSION: Rap1A may play certain roles in the development of azoospermia.

Adult↗

PubMed2004

[Clinical analysis of ultrasound-guided embryo transfer after in-vitro fertilization].

OBJECTIVE: To investigate whether ultrasound (US) guided embryo transfer could improve pregnancy rates. METHODS: A prospective randomized trial was conducted to compare embryo transfer under abdominal US guidance (n = 178) with traditional embryo transfer (n = 152). RESULTS: The clinical pregnancy rate was 37.1% (66/178) in the US group compared with 25.0% (38/152) in the traditional group (P < 0.05). CONCLUSIONS: US guided embryo transfer after in vitro fertilization increased pregnancy and implantation rates. It is suggested that embryo transfer should be performed under ultrasound guidance.

Adult↗

PubMed2004

Decreases of voltage-dependent K+ currents densities in ventricular myocytes of guinea pigs by chronic oxidant stress.

AIM: To determine the changes of delayed rectifier K(+) currents (I(k)) and inward rectifier K(+) currents (I(k1)) in the ventricular myocytes of guinea pigs during the gradual apoptotic process by the chronic oxidant stress treatment. METHODS: H(2)O(2) 50 micromol/L (24 h) was used for inducing apoptosis in the cardiomyocytes culture of neonatal rats and to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h. Apoptosis was evaluated by TUNEL methods and voltage-dependent K(+) currents were recorded by patch-clamp techniques. RESULTS: H(2)O(2) 50 micromol/L (24 h) induced cell apoptosis in the cardiomyocytes culture of neonatal rats. This concentration was used to treat the isolated ventricular myocytes of adult guinea pigs in vitro for 24 h and the voltage-dependent K(+) currents densities (I(k), I(k1)) were down-regulated. The densities of the delayed rectifier K(+) currents (I(k)) in 50 micromol/L H(2)O(2) group were 2.52+/-0.57 pA/pF vs 5.73+/-1.84 pA/pF in the control group at +50 mV (n=8, P<0.01). The densities of the inward rectifier K(+) currents (I(k1)) in 50 micromol/L H(2)O(2) group were -13.9+/-2.70 pA/pF, 2.52+/-0.57 pA/pF vs -59.7+/-11.9 pA/pF, 5.73+/-1.84 pA/pF in the control group at -120 mV (n=8, P<0.01) and -40 mV (n=8, P<0.05), respectively. The extent of inward rectifier property of I(k1) was weakened by 50 micromol/L H(2)O(2) treatment. CONCLUSION: The densities of I(k), I(k1) in the cardiomyocytes of guinea pigs were down-regulated and the inward rectifier property of I(k1) was weakened during the gradual apoptotic process after 50 micromol/L H(2)O(2) treatment for 24 h.

Animals↗

PubMed2004

[Expression and its significance of b-FGF in human benign prostatic hyperplasia and prostatic carcinoma tissues].

AIM: To investigate the clinical significance of basic fibroblast growth factor (b-FGF) in human benign prostatic hyperplasia (BPH) and prostatic carcinoma (Pca). METHODS: b-FGF expressions were examined by RNA dot blot hybridization and immunohistochemical staining in prostate tissues from 40 normal cases (NP), 38 BPH and 36 Pca. RESULTS: The expressions of b-FGF in BPH and Pca tissues were significantly higher than those in normal prostate tissues (P < 0.01). There was no significant correlation between the increased expression of b-FGF and the graduation of BPH, pathologic grading as well as clinical stages of Pca. CONCLUSION: b-FGF may be secreted from BPH and Pca tissues themselves, which is closely involved in the genesis and development of BPH and Pca.

Aged↗

PubMed2004

[Construction and expression of anti-human CD3 single chain Fv antibody/human p53 tetramerization domain fusion gene].

AIM: To construct anti-human CD3 single chain Fv antibody (scFv)/human p53 tetramerization domain fusion gene and express the fusion protein in Hela cells. METHODS: The anti-human CD3 scFv was cloned into the previously constructed plasmid pUC18/IgG3/p53 to construct anti-human CD3 scFv /human p53 tetramerization domain fusion gene. After enzyme digestion analysis and sequencing, the fusion gene was subcloned into the expression plasmid pSecTag2-B. Then the plasmid pSecTag2-B containing the fusion gene was transfected into Hela cells. The expressed products were analyzed by SDS-PAGE and Western blot. The binding of the purified fusion protein to human peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. RESULTS: DNA sequencing showed the fusion gene was constructed successfully. The expressed product of the fusion gene with a relative molecular mass (M(r)) about 35 000 was confirmed by SDS-PAGE and Western blot. The purified tetrameric anti-human CD3 scFv showed significantly stronger binding to PBMCs than scFv. CONCLUSION: The tetrameric anti-human CD3 scFv which can bind to PBMCs has been successfully expressed and purified for potential use in clinical studies.

CD3 Complex↗

PubMed2004

[Effects of cyclovirobuxine D on intracellular Ca2+ and L-type Ca2+ current in rat ventricular cardiomyocytes].

AIM: To determine the effects of cyclovirobuxine D (CD) on intracellular Ca2+ mobilization and L-type Ca2+ current (I(Ca-L)) in isolated rat cardiomyocytes. METHODS: The effects of CD on the amplitude of I(Ca-L) and intracellular Ca2+ mobilization induced by KCl and caffeine were studied with the method of patch-clamp technique and laser scanning confocal microscopy in rat ventricular myocytes. RESULTS: CD decreased the amplitude of I(Ca-L) in a concentration-dependent manner. At 10 mV, 1 and 10 micromol x L(-1) CD decreased I(Ca-L) density from (- 9.9 +/- 1.8) pA/pF to (-6.4 +/- 1.4) and (-4.2 +/- 0.6) pA/pF, respectively. Confocal experiments showed that intracellular fluorescent intensity (FI) value of [Ca2+] in control resting level was not changed by 1 and 10 micromol x L(-1) CD. [Ca2+] increase in response to KCl could not be reduced by CD. The rise of [Ca2+]i in response to caffeine was further enhanced by pretreatment with CD. CONCLUSION: CD decreased I(Ca,L) in a concentration-dependent manner and increased [Ca2+]i release induced by caffeine in rat ventricular cardiomyocytes.

Animals↗

PubMed2004

[Inhibitory effect of RNA interference on expression of HPV16 E6 oncogene in cervical cancer cell line CaSki].

BACKGROUND & OBJECTIVE: Tumorigenesis and progression of cervical cancer closely relate with human papilloma virus (HPV) E6 and E7 oncogenes. Ribozyme and antisense oligonucleotides had been used to inhibit the expression of HPV E6 or E7 oncogenes to treat cervical cancer, but problems, including low efficiency, short-period maintenance, hard work, and high costs, still exist. This study was to evaluate the specific inhibitory effect and time-efficiency of RNA interference (RNAi) on HPV16 E6 gene in cervical cancer cell line CaSki. METHODS: The specific small interfering RNA (siRNA) of HPV16 E6 modified by fluorescein was synthesized, and transfected into CaSki cells. The transfection efficiency of siRNA was evaluated by calculating the ratio of fluorescent cells to total cells. Cell apoptosis was evaluated by flow cytometry (FCM). The mRNA level of HPV16 E6 before and after siRNA transfection was measured by RT-PCR, and protein level of HPV16 E6 was measured by Western blot and FCM. RESULTS: The transfection efficiency of siRNA was 81%. Apoptosis rates of CaSki cells at 1, 2, 5, and 9 d after transfection were 7.7%, 11.8%, 37.4%, and 12.6%, respectively. The mRNA level of HPV16 E6 at 1, 2, 5, and 9 d after transfection reduced by 77%, 83%, 59%, and 41%, respectively, but the mRNA level of beta-actin, as internal control, had no change. The inhibition rates of HPV16 E6 protein at 1, 2, 5, and 9 d after transfection were 79.7%, 80.4%, 71.3%, and 57.4%, respectively, but the protein level of Lamin A/C, as internal control, had no change at each time point. CONCLUSION: RNAi exists in CaSki cells, and has specific high efficiency on HPV16 E6 gene.

Actins↗

PubMed2004

[Relationship between the reduction of FHIT expression and the development of cervical carcinoma].

OBJECTIVE: To explore the relationship between reduction of FHIT expression of fragile histidine triad (FHIT) and the development of cervical carcinoma. METHODS: Expression of the FHIT product was detected by immunohistochemistry in 22 normal cervices and 35 cervical intra-epithelial neoplasias (CINs) as well as 60 primary invasive cervical carcinomas. RESULTS: The rates for loss or reduction of expression of FHIT protein in the squamous epithelium of normal cervices, CIN I-II, CIN III and noninvasive carcinoma and invasive cervical carcinoma were 0% (0/22), 20% (4/20), 53.3% (8/15), 81.7% (49/60) respectively (P<0.05). Among the well differentiated, intermediately differentiated and poorly differentiated invasive cervical carcinoma, the rates for loss or reduction of expression of FHIT protein were 60.0% (6/10), 70.0% (14/20), and 96.7% (29/30) respectively (P<0.05). The rate of the impaired FHIT protein expression in the invasive cervical carcinoma with lymph node metastasis (90.9%) was higher than that without lymph node metastasis (79.6%). CONCLUSION: The impaired FHIT protein expression might be a useful indicator in identifying the possibility of the progression of advanced CINs into invasive cervical carcinoma. FHIT protein expression might indicate the clinical characteristic of cervical carcinoma cells and the prognosis of cervical carcinoma.

Acid Anhydride Hydrolases↗

PubMed2004

[Experimental study on the penetrability of trypan blue to the rat prostate].

OBJECTIVE: To understand the penetrability of trypan blue to the normal prostate as well as to the inflammatory prostate and the prostate with benign hyperplasia in rats. METHODS: Sixty SD male rats were randomized into 4 groups: NP (normal prostate) group (n = 15), BP (bacterial prostatitis) group (n = 15), BPH (benign prostatic hyperplasia) group (n = 15), and BPH-BP (benign prostatic hyperplasia with bacterial prostatitis) group (n = 15). Five rats were taken from each group as non-staining controls (NC, n = 5 x 4) and the other 10 were injected by tail intravenation with 1% trypan blue and then the prostates were isolated from the rats killed by anaesthesia after 2 hours. The color of the prostates and other tissues of the animals were observed and the contents of the trypan blue in the tissues of the prostates were determined separately by colorimetry. RESULTS: Apart from the tissues of brains and spinal cord the surface and the inner tissues of the prostates with NP, BP, BPH and BPH-BP from the rats injected with the dye were also dyed blue similar to that of the muscles, livers, intestines and others. The content of the trypan blue in the tissues of the prostates with NP, BP and BPH-BP was obviously higher than those with NP and BPH. CONCLUSION: The penetrability of trypan blue with properties of ionization and larger molecular weight is high in either the normal prostate or the prostate with BP, BPH and BPH-BP, and much higher in inflammatory prostate than in the normal prostate and the prostate with BPH.

Animals↗

PubMed2003

An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria.

We constructed a peptide consisting of a staphylococcal AgrD1 pheromone fused to the channel-forming domain of colicin Ia and named it pheromonicin. This fusion peptide had bactericidal effects against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively), but not against Staphylococcus epidermidis or Streptococcus pneumoniae. Growth rates, vital staining and colony forming unit (CFU) counts showed that pheromonicin did not merely suppress growth but killed S. aureus cells. The specificity of pheromonicin was shown by the absence of bactericidal effects against an accessory gene regulator (agr) locus knockout of S. aureus, and a dose-dependent inhibition of the bactericidal effects of pheromonicin by competition with corresponding free AgrD pheromone. In vivo, all pheromonicin-treated mice survived administration of MRSA that was lethal to controls. No toxicity was detectable in human liver or renal cells in culture, or in livers, kidneys or spleens of pheromonicin-treated mice. The results suggest that these types of chimeric peptides may be of value as antibiotics against specific bacterial infections.

Amino Acid Sequence↗

PubMed2003

[Construction and expression of anti-CD3/anti-prostate-cancer bispecific single-chain antibody].

OBJECTIVE: To construct a recombinant vector that expresses anti-CD 3/anti-prostate-cancer bispecific single-chain antibody (BsAb), and study its biological activities and clinical significance. METHODS: An anti-CD 3/anti-prostate-cancer BsAb was constructed by PCR and molecular biological technique of DNA cloning. The fusion gene, confirmed by sequencing, was subcloned into the pSectag2-B plasmid from the pUC18 vector by digestion with EcoR I and Hind III restriction endonucleases, whose sites exist in both the vectors. Then the recombinant plasmid was transfected into HeLa cells. The expression products in the supernatant were analyzed by both SDS-PAGE and Western blot technique, then were purified with Ni(2+)-NTA superflow affinity chromatography. Its biological activities were examined by flow cytometry (FCM). RESULTS: A fragment of 1.5 kb was inserted into the pUC18 vector, which was sequenced and verified to be identical with that designed. The expression of anti-CD 3 x anti-prostate-cancer BsAb yielded a soluble protein with an apparent molecular mass of 61 KD. The purification rate of the expressed BsAb was up to 90.537% and the yield of purified BsAb from this procedure was 0.09 mg/ml. The positive binding rates of BsAb to PBMC and to PC-3 cell were 54.1% and 53.7% respectively. CONCLUSION: The anti-CD 3 x anti-prostate-cancer BsAb thus constructed exhibits beneficial biological activities and may play an important role in the treatment of prostate cancer.

Antibodies, Bispecific↗

PubMed2003

Migration to a western country increases asthma symptoms but not eosinophilic airway inflammation.

The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11; P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms.

Adolescent↗

PubMed2003

Increased resistance of tumor cells to hyperthermia mediated by integrin-linked kinase.

PURPOSE: Integrin-linked kinase (ILK) is a serine-threonine kinase associated with anchorage-independent growth and tumorigenic transformation. Previous studies indicate that overexpression of ILK is common among several types of tumors, and it is involved in the regulation of tumor cell survival under stress. In this study, we examined the effects of ILK expression on tumor cellular response to hyperthermia. EXPERIMENTAL DESIGN: We used an adenovirus-mediated approach to overexpress the ILK gene in a prostate cancer cell line and examine its effects on heat stress-induced cell death. Clonogenic survival, as well as apoptosis, was evaluated in cells that overexpress ILK. In addition, the ability to form tumors in vivo was examined in syngeneic hosts. Finally, potential molecular mechanisms of ILK-mediated resistance to heat were examined by determining the status of a variety of signal transduction pathways. RESULTS: ILK overexpression made tumor cells significantly more resistant to the cell-killing effects of hyperthermia. This was correlated at the molecular level with the down-regulation of hyperthermia-induced activation of stress-activated protein kinase/c-Jun-NH(2)-terminal kinase, p38 mitogen-activated protein kinase activities, and caspase 9. The overexpression of ILK was also shown to induce a more rapid tumor growth in a murine prostate cancer cell line CONCLUSION: ILK plays an important role in tumor growth and tumor response to hyperthermia treatment.

Adenoviridae↗