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Biomedical subjects

Yang Cao

Publications and source records attributed to Yang Cao.

At least 73 records · Page 4Linked to original sources

Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders.

Muscarinic agonists might be useful in the treatment of neurological disorders, including Alzheimer's disease, schizophrenia, chronic pain, and drug abuse. Previous studies identified a series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine with high activity and selectivity for muscarinic receptors. To develop compounds with improved central nervous system penetration, several new derivatives were synthesized and characterized for muscarinic receptor binding and activity. One ligand (11) exhibited agonist activity at M(1), M(2), and M(4) receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.

Animals↗

Dissolution and mineralization behaviors of HA coatings.

The dissolution and mineralization behavior of HA coatings are two of the main factors governing the bioactivity of coatings. After different post treatment operators, the plasma-sprayed HA coatings have different characteristics, including different chemical composition, crystallinity, crystallite size and dissolution behavior. In this study, HA coatings were characterized by X-ray diffraction, scanning electron microscope, and Fourier transform infrared spectra before and after immersion in simulated body fluid (SBF). When immersed in SBF, both dissolution and precipitation occurred at the same time, but the kinetics of dissolution was quite different from that of precipitation. The former was dominated by ion exchange, while the latter was controlled by the ion concentration product and the solubility of the particles. Therefore, the dissolution behaviors of phosphate ions partly depended on the dissolution behaviors of calcium ions. With the increase of ions concentration in solution by dissolution, more nucleation sites appeared on the surface of coatings. Crystalline grains gradually grew up on the nucleation sites and developed into biomineral layers. The biomineral layers were the results of the precipitation of the ions in the solution; and the carbonates partially substituted phosphates to form bone-like apatite. The different dissolution characters resulted in quite different morphology of the biomineral layers: the coatings with low solubility induced biomineral layers of large grains; on the contrary, the biomineral layers of network structure were observed on the more soluble coatings.

Biomimetic Materials↗

[Correlation between prognosis and cell proliferation, apoptosis in squamous cell carcinoma of tongue].

OBJECTIVE: To study the correlation between prognosis and cell proliferation, apoptosis in squamous cell carcinoma (SCC) of tongue. METHODS: Using TdT-mediated dUTP biotin nick end labeling (TUNEL) for cell apoptosis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA), Bcl-2 and Bax protein expression. RESULTS: In SCC of tongue, the positive rates of apoptosis index (AI), Bcl-2, Bax and PCNA were 55.8%, 65.4%, 73.1% and 100.0% respectively. In the univariate Kaplan-Meier analysis, low expression of Bax, high expression of PCNA, Bcl-2/Bax expression ratio > 1 and high staging were all associated with lower survival rate (Log-rank test, P < 0.05, respectively), AI was only correlated with grading. Bcl-2 did not show a significant association with all features. CONCLUSIONS: The levels of Bax and PCNA expression and Bcl-2/Bax expression ratio have independent prognosis value in squamous cell carcinoma of the tongue. Comprehensive analysis of these parameters can be helpful to identify biological behavior and predict more accurately the prognosis of patients of tongue squamous cell carcinoma.

Adult↗

[Clinical application of a software for the analysis of arterial blood gases graph in 231 patients with chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the clinical significance of a computer software for the analysis of arterial blood gases graph (ABGG) in chronic obstructive pulmonary disease(COPD). METHODS: The software was developed with Win98 as the operating platform and the visual software Delphi 5.0 from Borland Company, and it was used for evaluation of the changes in arterial blood gases (ABG) of 231 COPD cases. RESULTS: (1) With the software it took only (4.7+/-0.5)s to draw and analyze an ABGG of COPD patients during oxygen inhalation; the time was much shorter than manual analysis (90.2+/-4.9)s, P<0.001. (2) During acute attack, the distributions of the arterial blood gases parameters on ABGG were as follows: 55.4% of cases in the area of insufficient ventilation and deranged gas exchange (area 5), 22.9% of cases in the area of compensated ventilation and deranged gas exchange (area 4), 21.6% of cases in the area of excessive ventilation and deranged gas exchange (area 6). (3) When the COPD patient's condition improved, the location of ABG in ABGG shifted from area 5 to area 4 or area 6. The distributions of the arterial blood gases parameters on ABGG of 106 cases on admission were significantly different from those at the time of discharge. (4) With deterioration of patient's condition, it shifted to area 5. Before death, the arterial blood gases parameters were exclusively in the area 5. CONCLUSION: The computer software for ABGG shortened the time to draw and evaluate ABG during oxygen inhalation, and it could reflect the changes in patient's condition promptly.

Aged↗

[Establishment of normal value of posterior arch length of adolescence in Chengdu].

OBJECTIVE: To investigate the development of third molar embryo and establish the normal value of posterior arch length of adolescence in Chengdu. METHODS: The samples consisted of 40 males and 41 females with Class 1 dentitions, normal second molar occlusion, no history of orthodontic treatment, and good facial balance. Cephalometry and statistic analysis were conducted for all the subject. RESULTS: The normal value of posterior arch length of maxilla in male was(16.52 +/- 2.35) mm and in female was(16.42 +/- 2.55) mm. The normal length of mandible was(13.00 +/- 2.44) mm in male and(12.43 +/- 2.18) mm in female. But statistic analysis showed no gender difference. Most of the third molar embryo had been formed and their tooth crowns had been calcified, the occurrence ratio was 84.0% in maxilla and 85.2% in mandible. Most of them located in the middle and inclined mesially. CONCLUSION: The data obtained in this study will be valuable for our clinical practice and be helpful for the study concerning dento-facial growth and development.

Adolescent↗

[Ambulatory pulse pressure and left ventricular hypertrophy in patients with essential hypertension].

OBJECTIVE: To evaluate the relationship between the left ventricular hypertrophy (LVH) and the ambulatory pulse pressure and aortic root dimension (AOD) in essential hypertensive patients. METHODS: We monitored the 24-hour ambulatory blood pressure and applied echocardiography in 107 essential hypertensive patients. Using the left ventricular mass index (LVMI) as an index in evaluating LVH, the patients were divided into 2 groups: 29 cases in the LVH group and 78 in the non-LVH group. RESULTS: The average levels of 24-hour pulse pressure, daytime pulse pressure, nighttime pulse pressure and AOD were significantly different between patients with LVH and without LVH (P < 0.05). Multiple stepwise regression analysis showed that the changes in nighttime pulse pressure and AOD were closely related to LVMI (P < 0.001). CONCLUSION: The pulse pressure and AOD are important factors leading to LVH in patients with essential hypertension.

Adult↗

[Long term follow-up results of Chinese prescription "Shen Yang" in the combined and sequential treatment of oral squamous cell carcinoma].

OBJECTIVE: To evaluate the long term therapeutic effect of Chinese prescription "Shen Yang" in the combined and sequential therapy for oral squamous cell carcinoma cases. METHODS: There are 238 cases with oral squamous cell carcinoma. They were divided into two groups randomly as "Shen Yang" experiment group and control group (placebo). 25 cases were precluded from the experiment group. 17 of them were due to unexperiment of taking "Shen Yang" within three months. 8 cases were lost of follow-up. 213 patients were included in this study. Among them, 104 cases in experiment group, and 109 cases in control one. Patients in both groups were followed-up for 5-10 years. Their life-curve was calculated by means of Logrank method. RESULTS: The survival rate of "Shen Yang" group was improved by 8.46%, 9.26%, 9.04% and 8.57% for 3-year, 5-year, 8-year and 10-year survival rates. But the differences between the two groups were not statistically significant (P=0.1936, P>0.05). CONCLUSION: Chinese prescription of "Shen Yang" had a tendency to improve the survival rate for oral squamous cell carcinoma patients.

Adult↗

[Research on spermatozoa-mediated gene transfer to product transgenic animals].

The recombinant plasmids pLNCXHLF fused with human lactoferritin gene were directly injected into male rabbit's testis and male goat's spermaductus. The transfected males were fertilized with females one month later.Using F(1)/R(1) PCR system and southern blotting,the transgenic positive rate of rabbit offsprings genomic DNA was 35%(11/31). From the PCR results of F(1)/R(1) and F(2)/R(2) system,the transgenic positive rate of genomic DNA of goat offsprings were 33.3% (4/12) and 25% (3/12) respectively. We prepared genomic DNA from 11 kinds of tissues of goat offsprings,which were tongue, lung,liver, muscle, skin,brain, gonad, spleen, intestines, heart, and kidney. The result of F(1)/R(1) PCR system indicated that the abilities to uptake exogenous DNA were various in different tissues; the positive signals of F(2)/R(2) PCR system were feebler than the ones of F(1)/R(1) PCR system,and the density of positive signals attributed to the amount of copies of exogenous DNA in the tissues. In this experiment,spermatozoa-mediated gene transfer can produce the transgenic animals after exogenous DNA being entrapped by liposome. But during the course of fertilization and the early process of embryo proliferation,the exogenous DNA had lost segments,partly integrated,or existed outside of genomic DNA. So the rate of chimera was relatively high. According to this result,this method is not only a simple and effective way to produce transgenic animals but also make references to other researchers to prepare transgenic mammals by this means.

English Abstract↗

[Correlation between blood pressure variability and left ventricular hypertrophy in patients with primary hypertension].

OBJECTIVE: To study the correlation between blood pressure variability (BPV) and left ventricular hypertrophy (LVH) in patients with primary hypertension. METHODS: We monitored the 24-hour ambulatory blood pressure and determined the left ventricular mass index (LVMI) by two dimensional echocardiography in 87 patients with primary hypertension (PH) and 26 normal controls. RESULTS: The LVMI in the PH patients was significantly higher than that in the controls. It was positively correlated to the average level of the 24-hour systolic blood pressure (24 h-SBP), nighttime systolic blood pressure (n-SBP), and nighttime diastolic blood pressure (n-DBP) (r = 0.183, P < 0.05; r = 0.275, P < 0.01; r = 0.243, P < 0.05, respectively). It was also negatively correlated to the 24-hour systolic blood pressure variability (24 h-SBPV) and the daytime systolic blood pressure variability (d-SBPV) (r = -0.253, P < 0.01; r = -0.186, P < 0.05, respectively). The 24 h-SBPV in the patients with LVH was significantly lower than that of those without LVH, but there was no significant difference in d-SBPV and n-SBPV between the PH patients with LVH and those without LVH. CONCLUSION: The 24 h-SBPV is valuable in predicting LVH in hypertension.

Adult↗

Many actions of cyclooxygenase-2 in cellular dynamics and in cancer.

Cyclooxygenase-2 (COX-2) is the inducible isoform of cyclooxygenase, the enzyme that catalyzes the rate-limiting step in prostaglandin synthesis from arachidonic acid. Various prostaglandins are produced in a cell type-specific manner, and they elicit cellular functions via signaling through G-protein coupled membrane receptors, and in some cases, through the nuclear receptor PPAR. COX-2 utilization of arachidonic acid also perturbs the level of intracellular free arachidonic acid and subsequently affects cellular functions. In a number of cell and animal models, induction of COX-2 has been shown to promote cell growth, inhibit apoptosis and enhance cell motility and adhesion. The mechanisms behind these multiple actions of COX-2 are largely unknown. Compelling evidence from genetic and clinical studies indicates that COX-2 upregulation is a key step in carcinogenesis. Overexpression of COX-2 is sufficient to cause tumorigenesis in animal models and inhibition of the COX-2 pathway results in reduction in tumor incidence and progression. Therefore, the potential for application of non-steroidal anti-inflammatory drugs as well as the recently developed COX-2 specific inhibitors in cancer clinical practice has drawn tremendous attention in the past few years. Inhibition of COX-2 promises to be an effective approach in the prevention and treatment of cancer, especially colorectal cancer.

Animals↗

Low and maternal-specific expression of p57KIP2 in hydatidiform mole and its clinical implication.

In situ hybridization was applied to locate and detect the expression of p57KIP2 in hydatidiform mole (5 cases of partial hydatidiform mole and 18 cases of complete hydatidiform mole) and normal villi (23 cases). The positive signals of p57KIP2 expression were analyzed by HPIAS-1000 Image-Analysis System. p57KIP2 was highly expressed in normal villi but showed distinct low expression in hydatidiform mole (P < 0.01). Furthermore, the locus of low expression of p57KIP2 accorded with the place where lesion of trophoblast occurred. Detection of p57KIP2 made it possible to study the genetics of hydatidiform mole at the transcriptional level. Low expression of p57KIP2 could be a molecular marker in hydatidiform mole and a target for therapy.

Cyclin-Dependent Kinase Inhibitor p57↗

Expression of c-erbB2 in gestational trophoblastic disease and its clinical significance.

In order to explore a potential indicator of predicting the occurrence and development of gestational trophoblastic tumor, the expression of c-erbB2 oncogene in human normal placenta, hydatidiform mole and choriocarcinoma was investigated. The expression of c-erbB2 was detected immunohistochemically by monoclonal antibody against the gene on the formalin-fixed paraffin sections of 21 hydatidiform moles, 21 invasive moles, 20 choriocarcinomas and 30 normal placentas. Results showed that the expression level of c-erbB2 was significantly higher in gestational trophoblastic tumor than in hydatidiform mole and normal placenta of midterm and term pregnancy (P < 0.05), while there was no significant difference between patients with gestational trophoblastic tumor of stage III, IV and those of stage I, II. It was demonstrated that overexpression of c-erbB2 may closely associated with malignant transformation of hydatidiform mole, not only providing important insight into pathogenesis of gestational trophoblastic tumor, but also having an important significance for the early diagnosis and early treatment of gestational trophoblastic tumor.

Biomarkers, Tumor↗

Insulin-like growth factor-I gene cloning and protein expression in bovine trabecular meshwork tissue and cells.

Whether cultured bovine trabecular meshwork cells and trabecular tissue ex vivo express insulin-like growth factor-I (IGF-I) messenger RNA (mRNA) and protein was investigated. Total RNA of cultured bovine trabecular meshwork cells as well as trabecular meshwork tissue freshly excised from bovine eyes was extracted, and reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect IGF-I mRNA. RT-PCR product was verified by sequencing. Immunohistochemical stain was used to detect IGF-I protein. The results showed that a single PCR amplified product was obtained, and the sequence was homologous to the known sequence.. IGF-I immunostain was positive in the cytoplasm of trabecular meshwork cells. It was concluded that trabecular meshwork cells produce IGF-I and contribute to the presence of IGF-I in trabecular meshwork microenvironment as well as aqueous humor. Trabecular meshwork cells were affected by IGF-I not only through paracrine, but also autocrine action. Whether abnormal down-regulations in IGF-I production may contribute to the pathogenesis of primary open-angle glaucoma and the possibility of promoting the autocrine action of IGF-I by trabecular meshwork cells to treat the disease is worth further investigation.

Animals↗

The late asthmatic response is linked with increased surface tension and reduced surfactant protein B in mice.

Pulmonary surfactant dysfunction may significantly contribute to small airway obstruction during the asthmatic response, but neither its exact role nor its regulation is clear. Surfactant function and composition was studied in an Aspergillus fumigatus (Af)-induced late-phase allergic airway response in sensitized BALB/c mice. The peak of Af-induced airway hyperresponsiveness in sensitized and challenged mice 24 h after allergen provocation coincided with a significant fall in surface activity of the pulmonary surfactant. The underlying changes included time-dependent elaboration of eotaxin and IL-5 followed by eosinophil influx into the airways. The height of airway inflammation and hyperresponsiveness was preceded by release of IL-4 and marked reductions in surfactant protein (SP)-B, a hydrophobic surfactant protein responsible for maintaining low surface tension of the lining fluid of distal air spaces. Furthermore, intratracheal administration of IL-4 significantly inhibited SP-B, indicating a regulatory role of this cytokine in the surfactant biophysical changes. Thus surfactant dysfunction induced by an IL-4-driven SP-B deficiency after allergen provocation may be an important part of the late asthmatic airway response.

Animals↗

Overexpression of dominant-negative mutant hepatocyte nuclear fctor-1 alpha in pancreatic beta-cells causes abnormal islet architecture with decreased expression of E-cadherin, reduced beta-cell proliferation, and diabetes.

One subtype of maturity-onset diabetes of the young (MODY)-3 results from mutations in the gene encoding hepatocyte nuclear factor (HNF)-1 alpha. We generated transgenic mice expressing a naturally occurring dominant-negative form of human HNF-1 alpha (P291fsinsC) in pancreatic beta-cells. A progressive hyperglycemia with age was seen in these transgenic mice, and the mice developed diabetes with impaired glucose-stimulated insulin secretion. The pancreatic islets exhibited abnormal architecture with reduced expression of glucose transporter (GLUT2) and E-cadherin. Blockade of E-cadherin-mediated cell adhesion in pancreatic islets abolished the glucose-stimulated increases in intracellular Ca(2+) levels and insulin secretion, suggesting that loss of E-cadherin in beta-cells is associated with impaired insulin secretion. There was also a reduction in beta-cell number (50%), proliferation rate (15%), and pancreatic insulin content (45%) in 2-day-old transgenic mice and a further reduction in 4-week-old animals. Our findings suggest various roles for HNF-1 alpha in normal glucose metabolism, including the regulation of glucose transport, beta-cell growth, and beta-cell-to-beta-cell communication.

Animals↗

Thyroid hormone receptor interacting protein 3 (trip3) is a novel coactivator of hepatocyte nuclear factor-4alpha.

Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. HNF-4alpha, which is a transcription factor expressed in pancreatic beta-cells, plays an important role in regulating the expression of genes involved in glucose metabolism. Thus, cofactors that interact with HNF-4alpha and modify its transcriptional activity might also play an important role in regulating the metabolic pathways in pancreatic beta-cells, and the genes of such cofactors are plausible candidate genes for MODY. In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. Human Trip3 cDNA contained an open reading frame for a protein of 155 amino acids, and the gene was expressed in both pancreatic islets and MIN6 cells. Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. These results suggest that Trip3 is a coactivator of HNF-4alpha. Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha.

Animals↗

Hepatocyte nuclear factor-1alpha modulates pancreatic beta-cell growth by regulating the expression of insulin-like growth factor-1 in INS-1 cells.

Maturity-onset diabetes of the young type 3 (MODY3) is characterized by impaired insulin secretion. Heterozygous mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha are the cause of MODY3. Transgenic mice overexpressing dominant-negative HNF-1alpha mutant in pancreatic beta-cells and HNF-1alpha knockout mice are animal models of MODY3. These mice exhibit defective glucose-stimulated insulin secretion and have reduced beta-cell mass and beta-cell proliferation rate. Here we examined the effect of HNF-1alpha on beta-cell proliferation by overexpressing a human naturally occurring dominant- negative mutation P291fsinsC in INS-1 cells under the control of doxycycline-induction system. INS-1 cells overexpressing P291fsinsC showed apparent growth impairment. The proliferation rate estimated by [(3)H]thymidine incorporation was significantly reduced in P291fsinsC-expressing INS-1 cells compared with noninduced or wild-type HNF-1alpha-overexpressing INS-1 cells. Growth inhibition occurred at the transition from G1 to S cell cycle phase, with reduced expression of cyclin E and upregulation of p27. cDNA array analysis revealed that the expression levels of IGF-1, a major growth factor for beta-cells, and macrophage migration inhibitory factor (MIF), a cytokine expressed in pancreatic beta-cells, were reduced in P291fsinsC-HNF-1alpha-expressing INS-1 cells. Although MIF seemed to have proliferative function, blockade of MIF action by anti-MIF antibody stimulated INS-1 cell proliferation, excluding its direct role in the growth impairment. However, addition of IGF-1 to P291fsinsC-expressing INS-1 cells rescued the growth inhibition. Our data suggest that HNF-1alpha is critical for modulating pancreatic beta-cell growth by regulating IGF-1 expression. IGF-1 might be a potential therapeutic target for the treatment of MODY3.

Animals↗

[Expression of insulin-like growth factor-I in bovine trabecular meshwork cells in vitro].

OBJECTIVE: To determine whether cultured bovine trabecular meshwork cells in vitro would express insulin-like growth factor-I (IGF-I). METHODS: Newborn bovine trabecular meshwork cells of the third passage were cultured in vitro. The whole RNA from 10(6) cells was extracted with Trizol reagent, and specific oligonucleotide primer pair and reverse transcription polymerase chain reaction (RT-PCR) were used for detection of IGF-I messenger RNA. Immunohistochemical stain was used to detect IGF-I protein. RESULTS: Cultured cells had the specific characteristics of bovine trabecular meshwork cells. A single RT-PCR amplified product whose sequence was homologous to the known sequence was obtained. IGF-I immunostain was positive. CONCLUSIONS: Trabecular meshwork cells may produce IGF-I. This finding strongly supports the possibility that IGF-I may affect trabecular meshwork cells through paracrine and autocrine mechanisms.

Animals↗