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Biomedical subjects

C Peng

Publications and source records attributed to C Peng.

At least 19 recordsLinked to original sources

Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines.

AIMS/HYPOTHESIS: Activin receptor-like kinase 7 (ALK7), a member of the type I receptor serine/threonine kinases of the TGF-beta superfamily, was recently reported to regulate cell proliferation and apoptosis. We hypothesised that ALK7 may play a role in modulating pancreatic beta cell proliferation and/or apoptosis. METHODS: We detected ALK7 expression in beta cells using RT-PCR, immunostaining and western blotting. Constitutively active, dominant negative or wild-type ALK7 was introduced into beta cells using adenoviral delivery. Proliferation was assessed using (3)H-thymidine incorporation and apoptosis was quantified using terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling detection, DNA degradation analysis and caspase-3 assays. RESULTS: Induction of constitutively active ALK7 in beta cells resulted in growth inhibition and enhanced apoptosis; no effect was seen with INS-1 cells expressing wild-type or dominant negative ALK7. Elevated glucose concentrations and fatty acid (palmitate) markedly increased expression levels of ALK7 transcripts and proteins in INS-1 and rat islets and increased beta cell apoptosis. Activation of ALK7 increased Smad2 phosphorylation, reduced protein kinase B (Akt) kinase activity and was associated with increased levels of the bioactive forms of caspase-3, whereas co-expression of constitutively active ALK7 with dominant negative Smad2 or constitutively active Akt significantly diminished ALK7-induced growth inhibition and apoptosis in INS-1 cells. Although overexpression of constitutively active Akt significantly reduced ALK7-induced growth inhibition and ALK7-enhanced beta cell apoptosis, ALK7-stimulated Smad2 phosphorylation was not affected. CONCLUSIONS/INTERPRETATION: These results suggest that the pancreatic beta cell apoptosis induced by ALK7 activation occurs via the activation of two distinct downstream pathways: the suppression of Akt activation and the activation of the Smad2-caspase-3 cascade.

Activin Receptors, Type I↗

A model validation and consensus building environment.

Over half of the failures in drug development are due to problems with the absorption, distribution, metabolism, excretion, and toxicity, or ADME/Tox properties of a candidate compound. The utilization of in silico tools to predict ADME/Tox and physicochemical properties holds great potential for reducing the attrition rate in drug research and development, as this technology can prioritize candidate compounds in the pharmaceutical R&D pipeline. However, a major concern surrounding the use of in silico ADME/Tox technology is the reliability of the property predictions. Bio-Rad Laboratories, Inc. has created a computational environment that addresses these concerns. This environment is referred to as KnowItAll. Within this platform are encoded a number of ADME/Tox predictors, the ability to validate these predictors with/without in-house data and models, as well as build a 'consensus' model that may be a much better model than any of the individual predictive model. The KnowItAll system can handle two types of predictions: real number and categorical classification.

Databases, Factual↗

Arsenic removal from high-arsenic water by enhanced coagulation with ferric ions and coarse calcite.

Arsenic removal from high-arsenic water in a mine drainage system has been studied through an enhanced coagulation process with ferric ions and coarse calcite (38-74 microm) in this work. The experimental results have shown that arsenic-borne coagulates produced by coagulation with ferric ions alone were very fine, so micro-filtration (membrane as filter medium) was needed to remove the coagulates from water. In the presence of coarse calcite, small arsenic-borne coagulates coated on coarse calcite surfaces, leading the settling rate of the coagulates to considerably increase. The enhanced coagulation followed by conventional filtration (filter paper as filter medium) achieved a very high arsenic removal (over 99%) from high-arsenic water (5mg/l arsenic concentration), producing a cleaned water with the residual arsenic concentration of 13 microg/l. It has been found that the mechanism by which coarse calcite enhanced the coagulation of high-arsenic water might be due to attractive electrical double layer interaction between small arsenic-borne coagulates and calcite particles, which leads to non-existence of a potential energy barrier between the heterogeneous particles.

Arsenic↗

Study on hydration layers near nanoscale silica dispersed in aqueous solutions through viscosity measurement.

On the basis of the Einstein theory of viscosity of dispersion, a parameter, termed as solvation factor, is presented to evaluate the solvation degree of nanoscale particles dispersed in a liquid in this work. The value of the parameter is obtained through the measurements of relative viscosity of the dispersions as a function of the volume fraction of dry particles. The solvation factor has been used to study the hydration layers near nanoscale silica particles dispersed in water and aqueous electrolyte (NaCl and CaCl2) solutions in this work. The experimental results have shown that a strong hydration indeed applied to the silica surfaces in aqueous solutions, leaving a large volume of hydration layers on the surfaces. Also, it has been found that the hydration of the nanoscale silica particles could be greatly enhanced if they were dispersed in aqueous NaCl or CaCl2 solutions, which might be attributed to that the hydrated cations (Na+ or Ca2+) bind onto the silica/ water interface and thus increase the volume of the hydration layers.

Journal Article↗

Secondary potential in electrodialysis membranes and the effect on permselectivity.

The most important factor in the electrodialysis (ED) process is the permselectivity of the ion exchange membranes, which permit not only the separation of cations and anions in a solution, but also the separation of ions with the same sign but different valences. In this work, the mechanism of the permselectivity has been studied through the measurement of the potentials at different planes of the membrane. The experimental results have shown that there was a secondary potential inside ion exchange membranes in an electrodialysis process. At the membrane side touched with dilute solution, this secondary potential enhanced the external electrical field, and thus speeded up the passage of the corresponding ions in the dilute solution through the membranes; at the membrane side touched with concentrated solution, the secondary potential was contrary to the external electrical field and thus counteracted it, which could be very helpful by preventing the ions in the concentrated solution from entering the membranes. Obviously, the existence of the secondary potential might play an important role in the permselectivity of ion exchange membranes in ED processes.

Journal Article↗

Biological nitrogen removal in SBR bypassing nitrate generation accomplished by chlorination and aeration time control.

A novel control strategy for biological nitrogen removal with high nitrite built-up through chlorine dosage was studied. In the biological nitrogen removal process operated in a bench-scale sequencing batch reactor, dose of chlorine of 0.2 mg/l in the form of sodium hypochlorite was applied after the COD was depleted. The aerobic phase switched to an anoxic phase shortly after the ammonium was completely biotically oxidized. Nitrite accumulation was stably achieved which was attributed to the chlorination and the lag-time of nitrification. With the time control, stable 100% conversion of nitrite could also be sustained even under the absence of chlorine for at least 20 days. The nitrite oxidizer should have been killed rather than been suppressed in this study. For engineering applications, the advantages of the nitrification/denitrification via nitrite can compensate the cost of chlorine dosage. Combined with the aeration time control, it is feasible to apply chlorination in a biological nitrogen removal process in SBRs.

Bioreactors↗

Risk assessment approach for untreated wastewater using the QUAL2E water quality model.

This paper presents a novel approach for assessing the risk of consumer product ingredients in surface waters that receive untreated wastewater. The approach utilizes the water quality simulation model QUAL2E for predicting the impact caused by conventional pollutants, as well as the exposure concentration of consumer product ingredients. This approach invokes an impact zone concept whereby the receiving water can be thought of as a natural wastewater treatment system. After the river has recovered via self-purification, the ecosystem is then assessed by traditional risk assessment methods. This approach was validated using data collected from the Balatuin River, which is located in the Philippines. Results from this study support the use of QUAL2E for assessing the risk of consumer product ingredients in riverine systems receiving untreated wastewater.

Animals↗

Multi-wavelength mid-infrared micro-spectral imaging using semiconductor lasers.

Infrared (IR, 3-12-microm) microscopic spectral imaging is an important analytical technique. Many current instruments employ thermal IR light sources, which suffer the problem of low brightness and high noise. This paper evaluates the system engineering merit in using semiconductor lasers, which offer orders-of-magnitude-higher power, brightness, and lower noise. A microscopic spectral imaging system using semiconductor lasers (quantum cascade) as illuminators, and focal plane array detectors demonstrated a high signal-to-noise ratio (> 20 dB) at video frame rate for a large illuminated area. The comparative advantages of laser vs. thermal light source are analyzed and demonstrated. Microscopic spectral imaging with fixed-wavelength and tunable lasers of 4.6-, 5.1-, 6-, and 9.3-microm wavelength was applied to a number of representative samples that consist of biological tissues (plant and animal), solid material (a stack of laminated polymers), and liquid chemical (benzene). Transmission spectral images with approximately 30-dB dynamic range were obtained with clear evidence of spectral features for different samples. The potential of more advanced systems with a wide coverage of spectral bands is discussed.

Animals↗

The hygroscopic properties of dicarboxylic and multifunctional acids: measurements and UNIFAC predictions.

The role of water-soluble organic compounds on the hygroscopic properties of atmospheric aerosols has recently been the subject of many studies. In particular, low molecular weight dicarboxylic acids and some multifunctional organic acids have been found or are expected to exist in atmospheric aerosols in urban, semiurban, rural, and remote sites. Unlike for their inorganic counterparts, the hygroscopic properties of organic acids have not been well characterized. In this study, the hygroscopic properties of selected water-soluble dicarboxylic acids (oxalic acid, malonic acid, succinic acid, and glutaric acid) and multifunctional acids (citric acid, DL-malic acid, and L-(+)-tartaric acid) were studied using single droplets levitated in an electrodynamic balance at 25 degrees C. The water activities of bulk samples of dilute solutions were also measured. Solute evaporation was observed in the dicarboxylic acids but not in the multifunctional acids. Oxalic acid, succinic acid, and glutaric acid droplets crystallize upon evaporation of water, but, except for glutaric acid droplets, do not deliquesce even at 90% relative humidity (RH). Mass transfer limitation of the deliquescence process was observed in glutaric acid. Neither crystallization nor deliquescence was observed in malonic acid, citric acid, DL-malic acid, or L-(+)-tartaric acid. Malonic acid and these three hydroxy-carboxylic acids absorb water even at RH much lower than their respective deliquescence RH. The growth factor (Gf), defined as the ratio of the particle diameter at RH = 10% to that at RH = 90%, of oxalic acid and succinic acid was close to unity, indicating no hygroscopicity in this range. The remaining acids (malonic acid, glutaric acid, citric acid, malic acid, and tartaric acid) showed roughly similar hygroscopicity of a Gf of 1.30-1.53, which is similar to that of "more hygroscopic" aerosols in field measurements reported in the literature. A generalized equation for these four acids, Gf = (1-aw)-0.163, was developed to represent the hygroscopicity of these acids. Water activity predictions from calculations using the UNIFAC model were found to agree with the measured water activity data to within 40% for most of the acids but the deviations were as large as about 100% for malic acid and tartaric acid. We modified the functional group interaction parameters of the COOH(-H20, OH-H20, and OH-COOH pairs by fitting the UNIFAC model with the measured data. The modified UNIFAC model improves the agreement of predictions and measurements to within 38% for all the acids studied.

Aerosols↗

Changes in forest biomass carbon storage in China between 1949 and 1998.

The location and mechanisms responsible for the carbon sink in northern mid-latitude lands are uncertain. Here, we used an improved estimation method of forest biomass and a 50-year national forest resource inventory in China to estimate changes in the storage of living biomass between 1949 and 1998. Our results suggest that Chinese forests released about 0.68 petagram of carbon between 1949 and 1980, for an annual emission rate of 0.022 petagram of carbon. Carbon storage increased significantly after the late 1970s from 4.38 to 4.75 petagram of carbon by 1998, for a mean accumulation rate of 0.021 petagram of carbon per year, mainly due to forest expansion and regrowth. Since the mid-1970s, planted forests (afforestation and reforestation) have sequestered 0.45 petagram of carbon, and their average carbon density increased from 15.3 to 31.1 megagrams per hectare, while natural forests have lost an additional 0.14 petagram of carbon, suggesting that carbon sequestration through forest management practices addressed in the Kyoto Protocol could help offset industrial carbon dioxide emissions.

Biomass↗

Smads in human trophoblast cells: expression, regulation and role in TGF-beta-induced transcriptional activity.

Smad proteins have recently been shown to be downstream signaling molecules that transduce TGF-beta signals from cell surface to the nucleus. To determine the mechanisms of TGF-beta action in human trophoblast cells, we investigated the expression and regulation of Smad2,3,4, and 7 mRNAs in a normal trophoblast cell line, NPC, and a cell line derived from choriocarcinoma, JEG-3. Messenger RNAs for Smad2,3,4 and 7 were detected in both NPC and JEG-3 cells. TGF-beta1 induced modest increases in Smad2 and Smad4 mRNA levels without affecting Smad3 mRNA expression in both cell lines. Significant increases in Smad7 mRNA levels in both NPC and JEG-3 cells following TGF-beta1 treatment were observed. TGF-beta1 also induced promoter activity of the Smad7 gene, indicating a direct effect at the level of gene transcription. The transcriptional activity of TGF-beta was examined in JEG-3 cells using two TGF-beta responsive reporter constructs, p3TP-Lux and pAR3-Lux. We found that Smad3 and to a lesser extent, Smad2 and Smad4, enhanced, while Smad7 inhibited, TGF-beta1-induced transcriptional activities. The basal and TGF-beta1-induced transcription can be blocked by overexpression of a dominant negative TGF-beta type II receptor. Taken together, these findings demonstrate that in human trophoblast cell lines, the Smad pathway involved in TGF-beta signal transduction is functional and that TGF-beta plays an autocrine role in regulating gene expression.

DNA-Binding Proteins↗

Morphologic study and syntheses of type I collagen and fibronectin of human periodontal ligament cells cultured on poly(ethylene-co-vinyl alcohol) (EVA) with collagen immobilization.

The purpose of this study was to regenerate the human periodontal ligament (PDL) around dental implants by using a hybrid structure of cells with materials, such as PDL cells + collagen + poly(ethylene-co-vinyl alcohol) (EVA) on titanium implant. Human PDL cells were cultured on the EVA surface coated with type I collagen and the cell adhesion and extension were investigated. Furthermore, collagen type I and fibronectin syntheses were analyzed. The serum free culture was also tried, to investigate the role of collagen in detail. The results showed that: 1. Satisfactory adhesion, extension, and proliferation of the PDL cells on the EVA films coated with collagen were observed, but were not good without collagen. 2. Immunostaining of cultured PDL cells revealed the syntheses of type I collagen, when cultured on the EVA coated with collagen or conventional culture dish, though fibronectin synthesis was observed even in the EVA without collagen. 3. Only PDL cells on the EVA coated with collagen proliferated well in the absence of serum. These results indicate that our novel implant material (EVA coated with collagen) provides a possibility of PDL regeneration on dental implants.

Cell Culture Techniques↗

Expression of exon 13 from the Ki-67 gene in human cells and tissues by digoxigenin-labelled mRNA in situ hybridization.

OBJECTIVE: To get insight on the regulatory mechanism of Ki-67 gene expression in malignant cell cycle. METHODS: Non-radioactive in situ hybridization (ISH) was undertaken, combined with immunohistochemistry to study the Ki-67 gene transcription and translation in various human cells and tissues. HeLa cells and fresh colon cancer cells, tonsil, normal pancreas and pancreatic cancer tissues were used in this study. A 435 bp cDNA fragment located in exon 13 of the Ki-67 antigen gene was amplified by polymerase chain reaction (PCR). Digoxigenin-labelled antisense and sense RNA probes were prepared for detecting Ki-67 mRNA, combined with MIB-1 immunohistochemistry. RESULTS: Successful localization of Ki-67 mRNA in human HeLa cells, colon cancer cells, tissues specimen of the tonsil and pancreatic cancer tissue sections was accomplished by digoxigenin-labelling in situ hybridization technique. ISH to colon cancer cells and pancreatic cancer tissue slides showed that much stronger cytoplasm and perinuclear mRNA signals of the Ki-67 gene were present in malignant cells than in normal cells, which was in accordance with MIB-1 nuclear protein signals. CONCLUSIONS: A sensitive and practical in situ hybridization method for the analysis of Ki-67 antigen mRNA in human cell and tissue was developed. Abnormal transcription of exon 13 of Ki-67 gene might be responsible for malignant cell proliferation in colon and pancreatic cancer.

Digoxigenin↗

[Diagnosis and treatment of congenital biliary duct cyst: twenty-year experience].

OBJECTIVE: To summarize the experience in diagnosis and treatment of congenital biliary duct cyst. METHODS: Clinical data from 108 patients treated from 1980 to 2000 were analyzed retrospectively. RESULTS: Abdominal pain, jaundice and abdominal mass were presented in most pediatric patients. Clinical symptoms in adult patients were non-specific, resulting in delayed diagnosis frequently. Fifty-seven patients (52.7%) had coexistent pancreatic biliary disease. Carcinoma of the biliary duct occurred in 18 patients (16.6%). Ultrasonic examination was performed in 94 patients, ERCP in 46, and CT in 71. All of the patients were correctly diagnosed before operation. Abnormal pancreatobiliary duct junction was found in 39 patients. Before 1985, the diagnosis and classification of congenital biliary duct cyst were established by ultrasonography preoperatively and confirmed during operation. The main procedure was internal drainage by cyst-enterostomy. After 1985, the diagnosis was decided with ERCP and CT, the procedure was cyst excision with Roux-en-Y hepaticojejunostomy. In 1994, we used a new and simplified operative procedure to reduce the risk of malignancy of choledochal cyst. Retrograde infection of the biliary tract the major postoperative complication, could be controlled by the administration of antibiotics. CONCLUSIONS: The concept in diagnosis and treatment of congenital choledochal cyst has been changed greatly. CT and ERCP are of great help in the classification of the disease. Currently, cyst excision with Roux-en-Y hepaticojejunostomy is strongly recommended as the treatment of choice for patients with type I and IV cysts. Piggyback orthotopic liver transplantation is indicated for type V cysts (Caroli's disease) with frequently recurrent cholangitis, resulting in biliary cirrhosis.

Adolescent↗

Surface modification of poly(ethylene-co-vinyl alcohol) (EVA). Part I. Introduction of carboxyl groups and immobilization of collagen.

To enhance the surface biocompatibility of poly(ethylene-co-vinyl alcohol) (EVA) and high-density polyethylene (HDPE), carboxyl groups were introduced by ozone exposure. Type I collagen was immobilized onto the surface through polyion complexing. The carboxyl groups on the EVA were characterized by electron spectroscopy for chemical analysis and neutralization. The amounts of the carboxylic group and collagen increased with increases in time and temperature of exposure. Water-soluble fragments were produced by ozone exposure to EVA, and they acted as collagen crosslinkers. The differences in charge distribution of carboxyl groups affected the amount of collagen immobilization. Graft polymerization of acrylic acid was also carried out onto EVA and HDPE surfaces. The amount of collagen immobilized by graft polymerization was much higher than that by ozone exposure despite the introduction of almost the same amounts of carboxylic groups. It was suggested that the negative charge distribution influences the amount of collagen immobilized onto films.

Biocompatible Materials↗

Kinetics of DNA alkylation, depurination and hydrolysis of anti diol epoxide of benzo(a)pyrene and the effect of cadmium on DNA alkylation.

Anti benzo[a]pyrene diol epoxide (BPDE) alkylates guanines of DNA at N7 in the major groove and at the exocyclic amino group in the minor groove. In this report we investigated the rates of BPDE hydrolysis, DNA alkylation and subsequent depurination of BPDE-adducted pBR322 DNA fragment using polyacrylamide gel electrophoresis. Preincubation studies showed that it hydrolyzed completely in triethanolamine buffer in <2 min. The depurination kinetics showed that a fraction of the N7 alkylated guanine depurinated rapidly; however a significant amount of N7 guanine alkylation remained stable to spontaneous depurination over a 4-h period. Similar results were obtained for the hydrolysis and alkylation rates of syn isomer but it required nearly 500 times more concentration to induce similar levels of N7 guanine alkylation. Cadmium ion strongly inhibited the N7 guanine alkylation of both isomers. But the minor groove alkylation was not affected as demonstrated by postlabeling assay which confirmed the presence of heat-and cadmium-stable minor groove adducts in BPDE-treated calf thymus DNA. Based on these and our earlier findings, we propose a mechanism for the synergistic effect of cadmium in chemically induced carcinogenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Study of the hygroscopic properties of selected pharmaceutical aerosols using single particle levitation.

PURPOSE: To use a single particle levitation technique to investigate the equilibrium water sorption characteristics in both the evaporation and growth of four respiratory drugs at 37 degrees C: atropine sulfate (AS), isoproterenol hydrochloride (IPHC) and isoproterenol hemisulfate (IPHS) and disodium cromoglycate (DSCG). METHODS: The equilibrium water content was measured as a function of relative humidity (RH) by a single particle levitation technique using an electrodynamic balance (EDB). The change of water content was determined by the voltage required to balance the weight of the levitated particle electrostatically. The water activities of bulk samples were also measured. Growth ratios were determined and compared with values in the literature. RESULTS: Crystallization or deliquescence was not observed for AS, IPHC and IPHS. The hysteresis in the water cycle was not observed for any of the drugs. At RH approximately 0%, AS particles still contain about 5% water but IPHC and IPHS particles do not contain any residual water. The aerodynamic growth ratio from RH 0% to 99.5% is 2.60, 2.86, 2.42 and 1.26 for AS, IPHC, IPHS and DSCG, respectively. Supersaturated droplets of IPHC and IPHS are expected to exist in the ambient conditions. DSCG is in a solid state in the RH range of 10-90%. CONCLUSIONS: It is expected that some aerosolized drugs of low solubility may experience supersaturation before they enter the human body and this could exert a significant influence both on particle loss before inhalation and on the deposition of the drugs in the lungs. The EDB is a convenient and reliable tool for studying the hygroscopic properties of pharmaceutical aerosols, especially for supersaturated solutions.

Aerosols↗