Biomedical subjects
Publications and source records attributed to Bo Zhang.
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BACKGROUND: The effect of pitavastatin on the mRNA levels of apolipoprotein (apo) A-I, peroxisome proliferator-activated receptor alpha (PPARalpha), cholesterol 7alpha-hydroxylase (CYP7A1), and farnesoid X receptor (FXR) in HepG2 cells was examined to establish whether pitavastatin affects bile acid synthesis and if so, to determine a possible molecular mechanism. METHODS AND RESULTS: HepG2 cells were cultured in serum-free Dulbecco's modified Eagle medium for 18 h before drug treatment. Total RNA was extracted at set times and mRNA levels were quantified by reverse transcription-real time polymerase chain reaction. Pitavastatin at 0.1, 1, 5, and 10 micromol/L increased the mRNA levels of apo A-I, PPARalpha, CYP7A1, and FXR in a dose-dependent manner. The mRNA levels of apo A-I, PPAR alpha, CYP7A1, and FXR similarly increased with increasing doses of pitavastatin. Coincubation of mevalonate (4 mmol/L) with pitavastatin (5 micromol/L) reversed the inductive effects of pitavastatin on the mRNA levels of these genes, indicating that the inductive effects of pitavastatin were related to its inhibition of HMG-CoA reductase. CONCLUSIONS: Pitavastatin increased the mRNA levels of CYP7A1 in HepG2 cells, suggesting that increased conversion of cholesterol to bile acids may be the mechanism for its potent low-density lipoprotein cholesterol-lowering effects.
Background There is evidence that statins induce the regression of cardiac hypertrophy in a transgenic rabbit model of hypertrophic cardiomyopathy. Methods and Results The association between treatment with statins and the regression of cardiac mass (left ventricular mass index, LVMI) was investigated in a case - control study using transthoracic echocardiography in 304 patients with angina who underwent coronary angiography. Those who received pravastatin or simvastatin were defined as cases (n=66), and age, sex and body mass index-matched controls (n=127) were selected. The cases showed a significant decrease in LVMI compared with the controls. Although the cases included a significantly higher percentage of patients with hypertension and calcium antagonist (CaA) treatment than the controls, there were no relationships between LVMI and either hypertension or CaA treatment. Because the cases had a significantly higher number of stenosed vessels than the controls, LVMI for each number of stenosed vessels was analyzed, and a significant interaction effect between the association of LVMI with statin and the number of stenosed vessels was found. Conclusions Treatment with statins was associated with a lower cardiac mass in patients with angina, suggesting that this is one of the drugs' pleiotropic effects.
BACKGROUND: Cell adhesion molecules have been implicated in the adhesion of leukocytes to endothelial cells and therefore play a role in atherosclerosis, which is a frequent cause of morbidity and mortality in patients with coronary artery disease (CAD) or undergoing hemodialysis (HD). The levels of expression of leukocyte adhesion molecules were evaluated in patients with CAD or HD. METHODS AND RESULTS: The expression of leukocyte (ie, neutrophil, monocyte and lymphocyte) surface CD11a, CD18, intracellular adhesion molecule-1 (ICAM-1), very late antigen-4 alpha (VLA-4 alpha) and L-selectin was investigated by flow cytometry in 20 patients who were initially diagnosed with CAD (CAD group), 15 patients with coronary re-stenosed vessels (RESTE group), 20 undergoing HD (HD group) and 20 without CAD (CONT group). Monocyte surface expression of both CD11a and ICAM-1 in the CAD group was significantly higher than in the CONT group. Interestingly, when 15 patients with RESTE were analyzed, they showed monocyte CD11a and ICAM-1 expression levels comparable to those in the CONT group. On the other hand, there were no significant differences in the expression of CD11a, CD18, L-selectin or VLA-4 alpha between the HD group and CONT group, but monocyte L-selectin was increased in the CAD group compared with the CONT group. CONCLUSIONS: Because CD11a and CD18 are expressed on the cell surface as a heterodimer and ICAM-1 is a ligand for CD11a/CD18, this increased expression of CD11a and ICAM-1 may affect the development of initial atherosclerotic coronary stenosis, but not re-stenosis.
Four cases of intracranial schwannomas not arising from the stems of cranial nerves are reported. All cases were confirmed by surgery and pathological examination. The related histogenesis and the CT and MRI findings are discussed, and the literature is reviewed. The CT and MRI findings of these tumours were analysed retrospectively and their pathological characteristics were reviewed. The tumours presented as heterogeneous hypointense to isointense mixed dense lesions with multiple areas of cystic degeneration and necrosis. Extensive cystic degeneration was the prominent characteristic on CT. The tumours showed hypointense to isointense signal on T(1) weighted images and heterogeneous hyperintense signal on T(2) weighted images. On contrast enhanced CT and MRI, the solid component and the wall of the tumours showed moderate to strong enhancement. Haematoxylin and eosin staining of the lesion demonstrated two histological patterns, Antoni type A and Antoni type B. Immunostaining showed intense immunoreactivity for S-100 protein. The CT and MRI findings of these tumours were similar to those of schwannomas arising from cranial nerves, although the former show a higher rate of cystic degeneration. Therefore, even when a mass is not in the usual cranial nerve region, if its imaging characteristics are similar to those of common schwannomas, the possibility of a schwannoma not arising from cranial nerve should be considered.
Although endothelial dysfunction is associated with cardiovascular risk factors and is improved by cholesterol-lowering therapy, the relationship between endothelial function and cardiovascular risk factor profiles has not been fully investigated in coronary artery disease patients who have been treated with statins. We investigated endothelial function in male hypercholesterolemic patients (n=53) who underwent statin therapy over 6 months in a cross-sectional study. Patients were classified into three groups based on the results of coronary angiography: a normal coronary artery group (n=15), an angina pectoris group (n=20) and a myocardial infarction group (n=18). Endothelial function was assessed by measuring flow-mediated dilatation after reactive hyperemia in the brachial artery, and serum lipid, lipoprotein (a), glucose and insulin levels were measured. Significant associations were observed between the status of coronary disease and systolic blood pressure, lipoprotein (a), glucose and insulin levels (p <0.05, respectively), and the levels of these risk factors in the myocardial infarction group were higher than those in the other groups. Flow-mediated dilatation was also associated with the status of coronary disease (p <0.05), and the myocardial infarction group showed the lowest levels of flow-mediated dilatation (p <0.05). Flow-mediated dilatation was negatively correlated with systolic and diastolic blood pressures, serum levels of lipoprotein (a), glucose and insulin, and the status of coronary disease. Stepwise multiple regression analysis also revealed that lipoprotein (a), diastolic blood pressure and the status of myocardial infarction were significantly correlated with impaired vasodilatation. Serum lipids, age and smoking habit were independent of flow-mediated dilatation. In conclusion, even after cholesterol-lowering treatment, male patients with myocardial infarction still had endothelial dysfunction, and higher levels of lipoprotein (a) may be associated with endothelial dysfunction in such patients.
Many studies have established that dopamine (DA) secreted by tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus is the major inhibitory factor controlling prolactin (PRL) secretion from the anterior pituitary. Endogenous opioid peptides (EOPs), mainly the neuropeptide beta-endorphin, facilitate PRL secretion by decreasing TIDA neuronal inhibitory tone in a number of physiological conditions, including pregnancy and lactation. We have previously demonstrated that there are many more c-Fos-expressing neurons than TIDA neurons in the arcuate nucleus, and treatment with naloxone (NAL), an opioid antagonist, activated these neurons in pregnant rats. Our previous data also suggest that the rostral region of the arcuate nucleus is more important than the caudal region in regulating the nocturnal PRL surge in pregnant rats. The aim of this study was to investigate the effects of NAL in regulating TIDA neuronal activity and therefore facilitating PRL secretion during lactation in rats. NAL was continuously infused (0.2 mg/10 microL/min iv) for 1 h before the separated pups returned, and then for 2 or 5 h after the separated pups were returned. Radioimmunoassay (RIA) was used to measure plasma PRL levels, and the immunocytochemical (ICC) staining of c-Fos was performed to detect changes in transcriptional activity of neurons in the hypothalamus. ICC of tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis, was performed to visualize TIDA neurons in the arcuate nucleus. The results showed that the peak of the PRL response to suckling was markedly delayed and dampened in NAL-treated rats (p<0.05). The percentage of c-Fos positive TH neurons in the arcute nucleus increased in rats treated with NAL for 5 h after return of pups, but not in rats treated with NAL for 2 h.
The zinc finger transcription factor MTF-1 (metal-responsive transcription factor-1) is conserved from insects to vertebrates. Its major role in both organisms is to control the transcription of genes involved in the homeostasis and detoxification of heavy metal ions such as Cu2+, Zn2+ and Cd2+. In mammals, MTF-1 serves at least two additional roles. First, targeted disruption of the MTF-1 gene results in death at embryonic day 14 due to liver degeneration, revealing a stage-specific developmental role. Second, under hypoxic-anoxic stress, MTF-1 helps to activate the transcription of the gene placental growth factor (PIGF), an angiogenic protein. Recently we characterized dMTF-1, the Drosophila homolog of mammalian MTF-1. Here we present a series of studies to compare the metal response in mammals and insects, which reveal common features but also differences. A human MTF-1 transgene can restore to a large extent metal tolerance to flies lacking their own MTF-1 gene, both at low and high copper concentrations. Likewise, Drosophila MTF-1 can substitute for human MTF-1 in mammalian cell culture, although both the basal and the metal-induced transcript levels are lower. Finally, a clear difference was revealed in the response to mercury, a highly toxic heavy metal: metallothionein-type promoters respond poorly, if at all, to Hg2+ in mammalian cells but strongly in Drosophila, and this response is completely dependent on dMTF-1.
Murine embryonic stem (ES) cells are an ideal system for the research of directed differentiation in vitro. Long double-stranded RNA, which can induce RNA interference (RNAi) effectively in many organisms, has been shown to suppress target gene expression efficiently and specifically in undifferentiated ES cells. However, it cannot be used in differentiated ES cells due to unspecific inhibition of gene expression resulting from the activation of interferon pathway following differentiation. Using green fluorescent protein (GFP) as a reporter system, we show here that a short hairpin RNA (shRNA) expression vector driven by the murine U6 small nuclear RNA promoter can specifically induce potent gene knockdown effect (i.e., inhibit GFP expression specifically) when transfected transiently into ES cells. Furthermore, when the expression vector is stably integrated into the genome of the cell, it can still show specific RNAi effect, which can be maintained at least for 10 days. These transfected ES cells showed no obvious differences in the morphology or growth rate in culture compared with untransfected cells, suggesting that the activation of shRNA-directed RNAi did not affect the properties of ES cells and that the RNAi effect in ES cells is specific and persistent. Our results prove the feasibility of the U6 promoter-driven shRNA expression technique to be used to study the function of genes expressed in ES cells. These ES cells, after integration of the U6-based RNAi vector into their genome, could be used to generate gene knockdown mice.
OBJECTIVE: Early gestational mammalian fetuses possess the amazing ability to heal cutaneous wounds in a scarless fashion. Over the past years, scientists have been working to decipher the mechanisms underlying this regenerative repair. The remarkable phenotypic differences between fetal and adult healings behooves us to learn their characteristics in genetics, which represents potentially important mechanisms involved in wound repair observed in fetal versus adult tissues. In this sense, it is reasonable to construct subtractive cDNA library for future research. METHODS: Middle laparotomy and hysterotomy were performed on pregnant rabbits at 20-day gestation to expose the fetal back, and a longitudinal incision through the skin was made on the back of the fetus. The traumatized fetal skin was harvested 12 hours post-operation, the fetus control and traumatized adult skin specimens were taken at the same time. dscDNA was synthesized from total RNA of skin samples with SMART technology. Taking one of the three samples as Tester respectively and the other two as Drivers, we obtained 1 forward and 2 reverse hybridization products. After being amplified with selective polymerase chain reaction, the products were inserted into a vector, and then transferred into E. coli HB101. The colonies were screened afterwards. RESULTS: The wounded fetuses were alive for a long time even after birth. Every determinant step, such as RNA isolation, cDNA synthesis, Rsa I digestion, adaptor ligation and hybridization, was well-operated. Subtractive efficiency identification demonstrated that the suppression subtractive hybridization (SSH) was successful. Insertion into vector and transferring to E. coli were satisfactory. CONCLUSIONS: Instead of classic SSH, an improved SSH with 2 Drivers was applied for the experiment. Results confirmed that the improved program was reasonable and correct in both theory and practice. The subtractive cDNA library we have obtained is going to be used for future researches to reveal scarless healing related gene(s) and its (their) expression.
BACKGROUND: There were only 3 multiple myeloma (MM) cell lines established in China. In this study, we succeeded in establishing a novel MM cell line and analyzed its biological characteristics. METHODS: Mononuclear cells isolated from the peripheral blood (PB) and bone marrow (BM) of a patient with advanced MM (lambda light chain type) were cultured in medium. Cell morphology was analyzed by Wright-Giemsa-staining and cytochemical staining, immunophenotyping by flow cytometry and cytogenetic analysis by chromosome RHG-banding technique. Quantitative fluorescent polymerase chain reaction (PCR) was used to detect Epstein - Barr virus (EBV) DNA. RESULTS: The established cell line could survive and proliferate in the presence of feeder cells or conditioned medium. The cells secreted lambda light chain and were negative for EBV. The Wright-Giemsa-staining showed typical plasmablast or plasma cell morphology. The cytochemical staining of the cells showed the following reactivity patterns: positive for acid phosphatase, negative for myeloperoxidase. The immunoprofile of the cells was concordant with that of MM cells: positive for CD10, CD28, CD38, CD138, CD56, CD49d, CD44, CD54 and CD58, negative for CD19, CD40, CD95, CD95L, CD34, CD2 and CD5. The cytogenetic analysis showed complex chromosome abnormality of i (1q+), 8q+, 13q+, i (17q), i (18q) and +M. There was no difference in morphology, immunophenotype and cytogenetics between cells from PB and BM. CONCLUSIONS: An MM cell line secreting lambda light chain named CZ-1 was established. The cells from both PB and BM have the same biological characteristics.
INTRODUCTION: Carbon dioxide clearance can be improved by reducing respiratory dead space or by increasing the clearance of carbon-dioxide-laden expiratory gas from the dead space. Aspiration of dead space (ASPIDS) improves carbon dioxide clearance by suctioning out (during expiration) the carbon-dioxide-rich expiratory gas while replacing the suctioned-out gas with oxygenated gas. We hypothesized that ASPIDS would allow lower tidal volume and thus reduce exposure to potentially injurious airway pressures. METHODS: With 8 hemodynamically stable, normothermic, ventilated patients suffering severe chronic obstructive pulmonary disease we tested the dead-space-clearance effects of ASPIDS. We compared ASPIDS to phasic tracheal gas insufflation (PTGI) during conventional mechanical ventilation and during permissive hypercapnia, which was induced by decreasing tidal volume by 30%. The mean P(aCO(2)) reductions with PTGI flows of 4.0 and 6.0 L/min and during ASPIDS (at 4.0 L/min) were 32.7%, 51.8%, and 53.5%, respectively. Peak, plateau, and mean airway pressure during permissive hypercapnia were significantly lower than during conventional mechanical ventilation but PTGI increased peak, plateau, and mean airway pressure. However, pressures were decreased during permissive hypercapnia while applying ASPIDS. Intrinsic positive end-expiratory pressure also increased with PTGI, but ASPIDS had no obvious influence on intrinsic positive end-expiratory pressure. ASPIDS had no effect on cardiovascular status. CONCLUSIONS: ASPIDS is a simple adjunct to mechanical ventilation that can decrease P(aCO(2)) during conventional mechanical ventilation and permissive hypercapnia.
OBJECTIVE: To investigate the proliferation and plasticity of neural stem cells in situ in adult rats after cerebral infarction. METHODS: Cerebral infarction models of rats were made and the dynamic expression of bromodeoxyuridine (BrdU) and BrdU/polysialylated neural cell adhesion molecule (PSA-NCAM) were determined by immunohistochemistry and immunofluorescence staining. RESULTS: Compared with the controls, the number of BrdU-positive cells in the subventricular zone (SVZ) and hippocampus increased strikingly at day 1 (P < 0.05), reached maximum at day 7, and decreased markedly at day 14, but it was still elevated compared with that of the controls (P < 0.05); The number of BrdU-labeled with PSA-NCAM-positive cells increased strikingly at day 7 (P < 0.05), reached maximum at day 14, and markedly decreased at day 28, but it was still elevated compared with that of the controls (P < 0.05), and was equal to 60% of the number of BrdU-positive cells in the same period. CONCLUSIONS: Our results indicate that cerebral infarction stimulate the proliferation of inherent neural stem cells in situ and most proliferated neural stem cells represent neural plasticity.
BACKGROUND & OBJECTIVE: Abnormal apoptosis is one of the key factors for drug resistance of neoplasms. Smac, a novel gene involved in regulation of apoptosis,plays an important role in tumor cell apoptosis induced by chemotherapeutic drugs. This study was designed to explore the effects of overexpressed Smac gene on chemotherapeutic sensitivity of gastric cancer cell line. METHODS: By liposome GeneSHUTTLE-40, Smac gene was transfected into gastric cancer cell line MKN-45. Cellular Smac gene expression were determined by reverse transcription-polymerase chain reaction (RT-PCR)and Western blot analysis. Cisplatin (1, 5, 10 microg/ml), mitomycin C (0.1,1,10 microg/ml), and curcumin (10, 20, 40 micromol/L) were selected to treat untransfected and transfected MKN-45 cells. Cellular proliferation activities were assayed by tetrazolium bromide (MTT) colorimetry. The morphological changes of cancer cells were observed under inverted microscope. Cellular apoptosis was determined by Annexin V-FITC and propidium iodide staining flow cytometry. RESULTS: Compared with untransfected control group,Smac mRNA and protein levels in transfected MKN-45 cells were significantly increased (P< 0.01). The growth inhibition rates of MKN-45 cells treated with various concentration of cisplatin, mitomycin C, and curcumin on MKN-45 cells were increased by 10.10%-23.80% (P< 0.01), 10.01%-15.86% (P< 0.01), 11.28%-22.12% (P< 0.01), respectively, with the cells becoming round, obviously refracted, and fragmented. The cellular apoptosis rates were increased by 6.7%-20.2% (P< 0.01), 5.4%-13.2% (P< 0.01), and 10.6%-20.1% (P< 0.01), respectively. CONCLUSION: Transfection of extrinsic Smac gene results in its over-expression in MKN-45 cells,which could increase the chemotherapeutic sensitivity of MKN-45 cells.
OBJECTIVE: To explore the spatial distribution character of dengue fever and the change of Aedes' population, so as to provide macroscopical decision-making evidences of prevention and supervision on dengue fever. METHODS: (1) Collecting data on morbidity of dengue and supervision on vector's population in the corresponding period. (2) Drawing digitized map of Chaozhou in scale of 1:50,000, including elements of boundary, residential areas, road and traffic, altitude, water systems etc. (3) Measuring the latitude and longitude of center position of surveillance safes on the scene. (4) Processing spatial analysis by the ArcGIS 8.5 software. RESULTS: Distribution of Aedes showed spatial cluster in Chaozhou, while its density was related to the distance to the watersides. The closer to the watersides, the higher the density was. Map on spatial distribution showed that although the Aedes epidemic situation changed yearly, but primarily be kept in high, middle, low regions. Cross-validation effects of the distribution maps were satisfactory. CONCLUSION: Geographic information system was promising in analyzing data on dengue fever, and better than other routine research methods.
The concentration and source of heavy metals in Nanjing urban soils and their relationships with soil properties were studied. The results indicated that the soils in Nanjing urban were not obviously polluted by Fe, Ni, Co and V, but polluted by Mn, Cr, Cu, Zn, and Pb to a certain extent. The heavy metals were irregularly distributed in soil profiles. Fe, Ni, Co, and V were originated from soil materials, but Cu, Zn, Pb, and Cr were anthropogenic input. Probably, Mn had different origins in different soils. There were positive correlations among Fe, Cr, Ni, Co, and V concentration, and among Cu, Zn, Pb, and Cr concentration. The Fe, Co, V, and Ni concentration were positively correlated with soil clay content and CEC, and the Cu, Zn and Pb concentration were negatively correlated with clay content. There were positive correlations between Cu, Zn, Pb and Cr concentration and organic C content, and between Pb concentration and soil pH.
Piezoelectric quartz crystal biosensor is a new sensor developed with the comprehensive utilization of the high sensitivity to mass and the surface characteristics of quartz crystal such as density, viscosity, dielectric constant, conductance, and the high specificity of biologic identification molecules. It has the features of high sensitivity, high specificity, simple operation, high analysis speed, low cost, small size, on-line detection, etc. It can be of wide application in the areas of medical laboratory diagnosis, environment monitor, foods sanitary control and industrial production. In this paper, the fundamental principle, structure and its applications are reviewed.
OBJECTIVE: To investigate proliferation and differentiation of neural stem cells in adult rats after cerebral infarction. METHODS: Models of cerebral infarction in rats were made and the time-course expression of bromodeoxyuridine (BrdU), Musashi1, glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU and Musashi1 were used to mark dividing neural stem cells. GFAP and NeuN were used to mark differentiating neural stem cells. RESULTS: Compared with controls, the number of BrdU-labeled and BrdU-labeled with Musashi 1-positive cells increased strikingly 1 day after cerebral infarction; approximately 6 fold with a peak 7 days later; markedly decreased 14 days later, but was still elevated compared with that of controls; decling to the control level 28 days later. The number of BrdU-labeled with GFAP-positive cells nearly remained unchanged in the hippocampus after cerebral infarction. The number of BrdU-labeled with NeuN-positive cells increased strikingly 14 days after cerebral infarction, reached maximum peak in the hippocampus 28 days after cerebral infarction in rats. CONCLUSION: Cerebral infarction stimulate proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.